Nishikant Subhedar

• Indian Institute of Science Education and Research Pune

Neuropeptide cocaine- and amphetamine-regulated transcript peptide (CARTp) is known to play an important role in reward processing. The rats conditioned to intra-cranial self-stimulation (ICSS) showed massive upregulation of CART protein and mRNA in the vicinity of the electrode implanted to deliver the electric current directly at the lateral hypo...

Although the phenomenon of memory formation and recall associated with the use of psychotropic drugs has been extensively studied, mechanisms underlying memories for natural reward have not been clarified. Herein, we test the hypothesis that glutamatergic receptors in the dentate gyrus play a role in memories associated with sucrose. We used pellet...

The role of nitrergic system in modulating the action of psychostimulants on reward processing is well established. However, the relevant anatomical underpinnings and scope of the involved interactions with mesolimbic dopaminergic system have not been clarified. Using immunohistochemistry, we track the changes in neuronal nitric oxide synthase (nNO...

Croaking is a unique component of reproductive behaviour in amphibians which plays a key role in intraspecies communication and mate evaluation. While gonadal hormones are known to induce croaking, central regulation of sound production is less studied. Croaking is a dramatic, transient activity that sets apart an animal from non-croaking individua...

In spite of the profound impact anger has on human life, the underlying mechanisms are not clear. While the reasons for this gap in knowledge may be traced to the nonavailability of a suitable animal model, protocols aimed at generating anger-like emotions in rats have been tested. Hungry rats were allowed to see and smell food, but were denied acc...

Dynamic re-configuration of circuit function subserves the flexibility of innate behaviours tuned to physiological states. Internal energy stores adaptively regulate feeding-associated behaviours by integrating opposing hunger and satiety signals at the level of neural circuits. Across vertebrate lineages, the neuropeptides CART and NPY have potent...

The inability to extinguish learned fear is a hallmark of trauma- and stress-related disorders. A form of inhibitory learning called fear extinction is an effective way to treat these disorders. However, the neurobiology of fear extinction has not been clarified. The involvement of a dopaminergic pathway from the ventral tegmental area (VTA) to the...

Neuroadaptations in neurocircuitry of reward memories govern the persistent and compulsive behaviors. The study of the role of hippocampus in processing of reward memory and its retrieval is critical to our understanding of addiction and relapse. The aim of this study is to probe the epigenetic mechanisms underlying reward memory in the frame of de...

Strategies drawn at understanding the functional attributes of specific neural circuits often necessitate electrical stimulation and pharmacological manipulation at the same anatomical site. We describe a simple, inexpensive and reliable method to fabricate a bipolar electrode-cannula assembly for delivery of electric pulses and administration of n...

Coincident excitation via different sensory modalities encoding objects of positive salience is known to facilitate learning and memory. With a view to dissect the contribution of visual cues in inducing adaptive neural changes, we monitored the lever press activity of a rat conditioned to self-administer sweet food pellets in the presence/absence...

Dynamic re-configuration of circuit function subserves the flexibility of innate behaviours tuned to physiological states. Internal energy stores adaptively regulate feeding-associated behaviours by integrating opposing hunger and satiety signals at the level of neural circuits. Across vertebrate lineages, the neuropeptides CART and NPY have potent...

Modulation of sensory perception by homeostatic feedback from physiological states is central to innate purposive behaviors. Olfaction is an important predictive modality for feeding‐related behaviors and its modulation has been associated with hunger‐satiety states. However, the mechanisms mapping internal states to chemosensory processing in orde...

Neuropeptide cocaine‐ and amphetamine‐regulated transcript (CART) is known to influence the activity of the canonical mesolimbic dopaminergic pathway and modulate reward seeking behaviour. CART neurons of the lateral hypothalamus (LH) send afferents to the ventral tegmental area (VTA) and paraventricular thalamic nucleus (PVT) and these nuclei, in...

Reward induces activity-dependant gene expression and synaptic plasticity-related changes. Lysine-specific histone demethylase 1 (LSD1), a key enzyme driving histone modifications, regulates transcription in neural circuits of memory and emotional behavior. Herein, we focus on the role of LSD1 in modulating the expression of brain derived neurotrop...

Problem While the testes represent an immune privileged organ, there is evidence that systemic inflammation is accompanied by local inflammatory responses. We therefore examined if transient systemic inflammation caused any inflammatory and functional consequences in murine testes. Method of Study Using a single systemic administration of Toll‐lik...

Background Anger is one of the primary emotions that profoundly impacts our daily life. Although the neural basis of anger needs to be explored on high priority, the field has not sufficiently advanced, perhaps due to the lack of a suitable animal model. New method We fabricated arenas in which the hungry rat can see and smell food but can not con...

Apart from reproduction, estrogen influences a multitude of processes. Increase in estrogen levels in women is known to promote reward probably mediated via the melanocortin and dopamine systems. Reduced estrogen in post-menopausal women attenuates reward evoking the need for stimulation with greater rewarding salience. This is reflected in the wel...

Reward deficit, expressed as anhedonia, is one of the major symptoms associated with neuropsychiatric disorders, but the underlying maladaptations have not been understood. Herein, we test the hypothesis that the neuropeptide cocaine- and amphetamine-regulated transcript (CART) may participate in the process. The study is justified since the peptid...

Exposure of NMDA receptor antagonists during developmental stages leads to behavioral consequences like attention deficit hyperactivity disorder (ADHD). However, the underlying molecular mechanisms have remained poorly understood. Herein, we studied the phosphorylated Akt (pAkt) and caspase-3, the key regulators of neuronal cell survival/death, as...

While insulin secreted from pancreas plays a pivotal role in the control of glucose homeostasis, it also interacts with hypothalamic sites and negatively influences the energy balance. The present study was undertaken to reveal the functional interaction between cocaine- and amphetamine-regulated transcript (CART), a well-known anorexic peptide, an...

Background Modulation of sensory perception by homeostatic feedback from physiological states is central to innate purposive behaviours. Olfaction is an important predictive modality for feeding-related behaviours and its modulation has been associated with hunger-satiety states. However, the mechanisms mapping internal states to chemosensory proce...

Ethanol ingestion by a mother during pregnancy entails adverse consequences for her offspring. In this study, adult female rats were given access to ethanol from 8 days prior to mating to post-parturition weaning, and the effects on her offspring were evaluated. We investigated changes in the cocaine- and amphetamine-regulated transcript peptide (C...

Although olanzapine is highly efficacious and most widely used second generation antipsychotic drug, the success of treatment has been hampered by its propensity to induce weight gain. While the underlying neuronal mechanisms are unclear, their elucidation may help to target alternative pathways regulating energy balance. The present study was unde...

Paraventricular thalamic nucleus (PVT) serves as a transit node processing food and drug-associated reward information, but its afferents and efferents have not been fully defined. We test the hypothesis that the CART neurons in the lateral hypothalamus (LH) project to the PVT neurons, which in turn communicate via the glutamatergic fibers with the...

Although the role of cocaine- and amphetamine-regulated transcript peptide (CART) in modulating the mesolimbic reward pathway has been suggested, underlying cellular mechanisms have not been elucidated. Herein, we investigate the involvement of Gi/odependent protein kinase A (PKA)/extracellular signal-regulated kinase (ERK)/cAMP response element bi...

Exaggerated thoughts, diminished mood and impaired cognition are the hallmarks of the schizophrenia-like condition. These symptoms are attributed to the dysregulation of dopamine and glutamate signaling in the brain. Since cocaine- and amphetamine-regulated transcript peptide (CART) modulates actions of dopamine as well as glutamate, we tested the...

Although chronic nicotine administration does not affect memory, its withdrawal causes massive cognitive deficits. The underlying mechanisms, however, have not been understood. We test the role of cocaine- and amphetamine-regulated transcript peptide (CART), a neuropeptide known for its procognitive properties, in this process. The mice on chronic...

Innate fear is critical for the survival of animals and is under tight homeostatic control. Deregulation of innate fear processing is thought to underlie pathological phenotypes including, phobias and panic disorders. Although central processing of conditioned fear has been extensively studied, the circuitry and regulatory mechanisms subserving inn...

Innate fear is critical for the survival of animals and is under tight homeostatic control. Deregulation of innate fear processing is thought to underlie pathological phenotypes including, phobias and panic disorders. Although central processing of conditioned fear has been extensively studied, the circuitry and regulatory mechanisms subserving inn...

Rats with electrode implanted in the lateral hypothalamus (LH)-medial forebrain bundle (MFB) area actively engage in intracranial self-stimulation (ICSS). However, the neuronal substrate that translates the electrical pulses into the neural signals, and integrates the information with mesolimbic reward system, has remained elusive. We test the hypo...

Although cocaine- and amphetamine-regulated transcript peptide (CART) is detected in several cortical and subcortical areas, its role in higher functions has been largely ignored. We examined the significance of CART in memory formation and tested if the downstream actions of CART involve N-methyl-D-aspartate (NMDA) activated extra-cellular signal-...

Depression is a major comorbidity factor of diabetes and the outcome of one disorder influences the other. Our aim is to scrutinize the link between the two, if any. Since neuropeptide Y (NPY) system plays an important role in regulating central glucose sensing mechanisms, and also depression-related behavior, we test the involvement of NPY in the...

N-methyl-D-aspartate receptor (NMDAR) hypofunction and disturbed Ca2+ signaling play a central role in the pathophysiology of positive symptoms and cognition deficits in schizophrenia. Cocaine- and amphetamine-regulated transcript peptide (CART) is known to regulate both NMDAR and Ca2+ signaling and improves memory formation. With a view to test th...

Parkinson's disease (PD) is an age-related disorder characterized by a progressive degeneration of dopaminergic neurons of substantia nigra (SN). The neuropeptide cocaine- and amphetamine-regulated transcript (CART) is known to closely interact with the dopamine system and regulate psychomotor activity. We screened the effectiveness of CART in reve...

Although dysregulation of the dopaminergic mesolimbic system is generally considered central to addiction, the involvement of other circuits is increasingly being appreciated. An interaction between locus coeruleus (LC) noradrenergic neurons and the posterior ventral tegmental area (pVTA) dopaminergic system, in the processing of drug-triggered rew...

Binge eating (BE) disrupts feeding and subverts reward mechanism. Since cocaine- and amphetamine-regulated transcript peptide (CART) mediates satiety as well as reward, its role in BE justifies investigation. To induce BE, rats were provided restricted access to high fat sweet palatable diet (HFSPD) for a period of 4 weeks. Immunoreactivity profile...

Although modulatory effects of neuropeptide Y (NPY) on ethanol consumption are well established, its role in ethanol reward, in the framework of mesolimbic dopaminergic system, has not been studied. We investigated the influence of nucleus accumbens shell (AcbSh) NPYergic system on ethanol self-administration in posterior ventral tegmental area (p-...

Since cocaine‐ and amphetamine‐regulated transcript peptide (CART) mediates feeding as well as reward, we investigated its role in binge eating (BE), a clinical condition which disrupts satiety. BE was induced in rats by providing 2‐h access to high fat‐sweet palatable diet (HFSPD) on alternate days for 4 weeks. Effect of drug treatments on HFSPD i...

Abundance of cocaine- and amphetamine-regulated transcript (CART) neuropeptide in the limbic areas like the olfactory system, central nucleus of amygdala (CeA), ventral bed nucleus of stria terminalis (vBNST) and the hypothalamus suggests involvement of the peptide in emotive processing. We examined the role of CART in mediating fear, a strong emot...

We investigated the involvement of neuropeptide Y (NPY) in the modulation of cholecystokinin-4 (CCK-4) evoked anxiety and depression. Adult male mice were injected with vehicle, CCK-4, NPY, NPY Y1 receptor agonist [Leu31, Pro34]-NPY or antagonist BIBP3226 via intracerebroventricular (icv) route and then subjected to social interaction or forced swi...

The cocaine- and amphetamine-regulated transcript (CART) neuropeptide has been implicated in the neural regulation of energy homeostasis across vertebrate phyla. Using gene-specific in situ hybridization, we have mapped the distribution of the four CART mRNAs in the CNS of the adult zebrafish. The widespread neuronal expression pattern for CART 2 a...

Although the role of alpha-melanocyte stimulating hormone (α-MSH) in alcohol seeking behaviour in rats has been demonstrated, the underlying mechanisms are not understood. Herein, we test the hypothesis that α-MSH might have a permissive effect in promoting the reward action of ethanol. Rats were implanted with cannulae targeted at the posterior ve...

Cocaine- and amphetamine-regulated transcript peptide (CART) with its wide distribution in the brain of mammals has been the focus of considerable research in recent years. Last two decades have witnessed a steady rise in the information on the genes that encode this neuropeptide and regulation of its transcription and translation. CART is highly e...

To investigate the role of the melanocortin (MC) system in the framework of the central nucleus of the amygdala (CeA) in the differential effects of the adenosine receptor blocker caffeine on anxiety-like behavior, using the social interaction (SI) test. Caffeine was given intraperitoneally, alone or in combination with alpha-melanocyte-stimulating...

Allopregnanolone (ALLO), a gamma-aminobutyric acid (GABA) type A receptor active neurosteroid, elicits hyperphagic response in rodents. Since GABA-A receptors are present on the peptidergic neurons in the hypothalamus, we were interested in finding out if ALLO and neuropeptide cocaine- and amphetamine-regulated transcript (CART) interact and influe...

Although the interaction between endogenous neuropeptide Y (NPY) and opioidergic systems in processing of reward has been speculated, experimental evidence is lacking. We investigated the role of NPY, and its Y1 receptors, in the nucleus accumbens shell (AcbSh) in morphine induced reward and reinforcement behavior. Rats were implanted with cannulae...

The cocaine- and amphetamine-regulated transcript (CART) peptidergic system is involved in processing diverse neuronal functions in adult animals, including energy metabolism. Although CART is widely distributed in the brain of a range of vertebrates, the ontogeny of this system has not been explored. The CART-immunoreactive system in the zebrafish...

The opioid-mesolimbic-dopamine circuitry operates between ventral tegmental area (VTA) and nucleus accumbens (Acb) and serves as a major reward pathway. We hypothesized that the neuropeptide cocaine- and amphetamine-regulated transcript (CART) is involved in the natural reward action mediated by the circuitry. Therefore, the modulation of opioid-me...

Amphibian metamorphosis is characterized by rapid tissue remodeling and drastic changes in the body structure and function. Like other organs, olfactory system also undergoes a dramatic rearrangement as the animal experiences transition from aquatic to terrestrial habitat. Reactive oxygen species (ROS) are known to play an important role during anu...

Since estradiol exercises inhibitory effect on food intake, we wanted to find out if this influence of estradiol is mediated by cocaine- and amphetamine-regulated transcript peptide (CART), a well established anorectic agent in the brain. Ovariectomized (OVX) rats, replaced with estradiol to produce estrous-phase like conditions, showed a significa...

Agmatine, a multifaceted neurotransmitter, is abundantly expressed in the hypothalamic paraventricular nucleus (PVN). Our aim was to assess (i) the effect of agmatine on feeding behaviour and (ii) its association, if any, with neuropeptide Y (NPY). Satiated rats fitted with intra-PVN cannulae were administered agmatine, alone or jointly with (i) α₂...

The cocaine- and amphetamine-regulated transcript peptide (CART)-containing system in the forebrain of Clarias gariepinus was studied with immunocytochemistry. While the immunoreactivity was prominently seen in the neurons of the entopeduncular nucleus (EN) located in the ventral telencephalon, CART-immunoreactive fibers were widely distributed in...

The subcommissural organ (SCO) is a highly specialised circumventricular ependymal organ covering and penetrating the posterior commissure. The secretory products of the SCO condense to form Reissner's fiber (RF). Because of its extensive secretory activity and the chemical properties of its secretion, the organ functions as similar to the neurosec...

We investigated the involvement of cocaine- and amphetamine-regulated transcript peptide (CART) in spatial learning and memory. Rats were intracerebroventricularly injected with CART or CART-antibody, with or without intraperitoneal scopolamine, for a period of 4 days, during which they were subjected to the acquisition protocol in Morris water maz...

Cocaine- and amphetamine-regulated transcript peptide (CART) has a role in chronic pain, and also in the actions of selective serotonin reuptake inhibitors (SSRIs) employed in the treatment of neuropathic pain. Herein, we test the hypothesis that CART may mediate the anti-hyperalgesic effect of the SSRI, fluoxetine, in neuropathic rats. Sciatic ner...

Cocaine- and amphetamine-regulated transcript peptide (CART) is a major anorectic agent present in the hypothalamus. We investigated the possible role of CART in mammary cancer-induced anorexia and body weight loss in rats. Mammary carcinogenesis was induced in the female Sprague-Dawley rats by intraperitoneal injection of N-methyl-N-nitrosourea (M...

While nicotine treatment to rodents causes a transient anorexia and persistent weight loss, withdrawal produces hyperphagia and weight gain. Herein, we test the hypothesis that endogenous anorectic peptide cocaine- and amphetamine-regulated transcript (CART) may be involved in these nicotine triggered physiological disturbances. In acute study, an...

Although hyperphagia and body weight gain are well-recognized consequences of social isolation, the underlying mechanisms are not understood. The aim of this work is to test the possibility that the endogenous cocaine- and amphetamine-regulated transcript peptide (CART) may be involved in the process. Socially isolated rats were screened for increa...

The present study underscores the effect of serotonergic antagonist on alpha-melanocyte stimulating hormone (α-MSH) induced neuronal regeneration. Swiss-albino mice were subjected to experimental spinal cord injury (ESCI) and treated with serotonergic antagonist, ritanserin, alone or in combination with α-MSH, and the locomotor recovery was investi...

The annual sexual cycle of Clarias batrachus is divisible into resting (December-January), preparatory (February-April), prespawning (May-June), spawning (July- August), and postspawning (September-November) phases. The gonosomatic indices rose steadily through the preparatory and prespawning phases, peaked in the spawning phase, and were greatly r...

Although physical isolation of rats is known to cause anxiety- and depression-like symptoms, the underlying mechanisms are not fully understood. We have attempted to define the role of endogenous melanocortins (MC) in the manifestation of these symptoms. Weaning rats were socially isolated for 6 weeks and subjected to behavioral paradigms like elev...

Since allopregnanolone (ALLO) elicits anxiolytic-like action and increases neuropeptide Y Y1 (NPY Y1) receptors gene expression in the amygdala, we were interested in studying the involvement of NPY Y1 receptors in the anxiolytic-like actions of ALLO. The anxiety-like behavior was evaluated in mice using Vogel's conflict test (VCT), in which number...

The iodotyrosine dehalogenase1 (DEHAL1) enzyme is a transmembrane protein that belongs to the nitroreductase family and shows a highly conserved N-terminal domain. DEHAL1 is present in the liver, kidney and thyroid of mammals. DEHAL1 is known to act on diiodotyrosine (DIT) and monoiodotyrosine (MIT), and is involved in iodine recycling in relation...

Neuropeptide Y (NPY) is widely distributed throughout the brain and has been implicated in some of the actions of ethanol. The aim of the present study was to characterize the subtypes of NPY receptors in ethanol induced sedation, tolerance and withdrawal hyper-excitability. The loss of righting reflex paradigm was used to record the sleep duration...

We investigated the role of corticotropin-releasing factor type 2 (CRF(2)) receptors in acute, chronic and withdrawal effects of nicotine on feeding behavior in rats. Nicotine was injected intraperitoneally, whereas CRF, CRF(2) receptors agonist urocortin-1 or selective antagonist astressin2-B were administered directly into the hypothalamic parave...

Although morphine is a potent antinociceptive agent, its chronic use developed tolerance in neuropathic pain (NP). Furthermore, opioid antagonist naloxone attenuated the antinociceptive effect of neuropeptide Y (NPY). The present study investigated the role of NPY and NPY Y1/Y5 receptors in acute and chronic actions of morphine in neuropathic rats...

Immunocytochemical application of antibodies against nNOS to the brain sections of Clarias batrachus revealed intense immunoreactivity in several olfactory receptor neurons (ORNs), in their axons over the olfactory nerve, and terminals in the olfactory glomeruli. Several basal cells in the olfactory epithelium showed NOS immunoreactivity. Applicati...

Since long-term treatment with imipramine increases the neuropeptide Y (NPY) levels in the frontal cortex and hypothalamus, the possibility exists that the antidepressant action of imipramine may be mediated via the NPY Y1 receptors. Bilateral olfactory bulbectomy (OBX) resulted in hyperactivity (increased number of ambulation, rearing and grooming...

We investigated the role of neuropeptide Y Y(1) receptors in acute, chronic and withdrawal effects of nicotine with reference to feeding behavior. Rats were administered with nicotine, neuropeptide Y, neuropeptide Y Y(1) receptor agonist [Leu(31),Pro(34)]neuropeptide Y or antagonist BIBP3226 (N(2)-diphenylacetyl)-N-[(4-hydroxy-phenyl)-methyl]-D-arg...

We investigated the effect of cocaine- and amphetamine-regulated transcript (CART) peptide on depression-like behavior in socially isolated and olfactory bulbectomized (OBX) rats. Administration of CART (54-102) into the lateral ventricle (50-100 ng) or central nucleus of amygdala (CeA) (10-20 ng) caused significant decrease in immobility time in t...

Weight gain is a common outcome of antipsychotics therapy in schizophrenic patients. However, the underlying neuronal mechanisms are unclear. The present study was undertaken to investigate the role of GABA(A) receptors within the framework of nucleus accumbens shell (AcbSh) in haloperidol-induced hyperphagia and body weight gain in sated rats. In...

We studied the expression of sGnRH mRNA in the neurons of the nucleus preopticus (NPO) of the Indian major carp, Cirrhinus cirrhosus, and their correlation with the reproductive status of the fish. Non-radioisotopic in situ hybridization histochemistry protocol employing biotinylated-oligonucleotide probes complementary to salmon GnRH, cichlid GnRH...

We investigated the profile of CART immunoreactivity in some discrete hypothalamic nuclei following chronic ethanol treatment and withdrawal conditions. Adult, male, Sprague-Dawley rats were fed with liquid diet (pair-fed) or liquid diet containing ethanol (ethanol-fed) for 15 days. Thereafter, all the animals were given access to ethanol free nutr...

Cocaine- and amphetamine-regulated transcript (CART) and neuropeptide Y (NPY) are involved in the regulation of food intake, body weight, pituitary hormones, and reproduction. While CART and NPY occupy overlapping fields in the brain of mammals, little is known about the interaction between these peptide-containing systems in other vertebrates. We...

We investigated the involvement of alpha-melanocyte stimulating hormone (alpha-MSH) following acute, chronic and withdrawal treatments of ethanol with reference to depression. The degree of depression was evaluated using Porsolt's forced swim test. While intracerebroventricular (icv) alpha-MSH (100-400 ng/rat) dose-dependently increased the immobil...

We studied the involvement of cocaine- and amphetamine-regulated transcript peptide (CART) in the central nucleus of amygdala (CeA), lateral bed nucleus of the stria terminalis (BNSTl) and nucleus accumbens shell (AcbSh) in generation of ethanol withdrawal symptoms, with particular focus on anxiety-like behavior using a social interaction test. Adm...

Etifoxine (6-chloro-2-ethylamino-4-methyl-4-phenyl-4H-3,1-benzoxazine hydrochloride), a nonbenzodiazepine anxiolytic drug, potentiates GABA(A) receptor function perhaps through stimulation of neurosteroid biosynthesis. However, the exact mechanism of etifoxine action is not fully understood. In this study, we have assessed the possible role of GABA...

Ultrastructural localization of neuronal nitric oxide synthase (nNOS) in olfactory receptor neurons (ORNs) and immunohistochemical detection of the enzyme in forebrain, pituitary, and pineal were undertaken in the teleost Oreochromis mossambicus. Application of post-embedding immunoelectron microscopy revealed nNOS-labeled gold particles on the cil...

Major problem involved in treatment of chronic pain with morphine is the development of tolerance and dependence. Previous studies have demonstrated the participation of melanocortin (MC) system in the development of tolerance to antinociceptive effect of morphine. However, the impact of supraspinal MC4 receptors (MC4 R) modulation on this phenomen...

The aim of this study was to determine whether neuropeptide Y (NPY) immunoreactivity in the cells and fibers in the forebrain and pituitary of Clarias batrachus is linked to the annual reproductive cycle. A steady rise in luteinizing hormone (LH) immunoreactivity was seen in the pituitary through preparatory (February-April) and prespawning (May-Ju...

The organization of cocaine- and amphetamine-regulated transcript peptide (CARTp, 54-102) immunoreactivity was investigated in the brain of the catfish, Clarias batrachus. CARTp-immunoreactivity was observed in several granule cells of the olfactory bulbs, in dot-like terminals around mitral cells, and in the fibers of the medial olfactory tracts....

Target ablation [removal of the olfactory bulb (OBX)] induces apoptotic death of olfactory sensory neurons (OSNs) and an immune response in which activation and recruitment of macrophages (ms) into the olfactory epithelium (OE) occupy a central role. Ms phagocytose apoptotic neurons and secrete cytokines/growth factors that regulate subsequent prog...