Brian Dias

Publications (13) View all

• Article: Towards new approaches to disorders of fear and anxiety.

  Brian G Dias, Sunayana B Banerjee, Jared V Goodman, Kerry J Ressler
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  ABSTRACT: Fear and anxiety are debilitating conditions that affect a significant number of individuals in their lifetimes. Understanding underlying mechanisms of these disorders affords us the possibility of therapeutic intervention. Such clarity in terms of mechanism and intervention can only come from an amalgamation of research from human to animal studies that attempt to mimic the human condition, both of which are discussed in this review. We begin by presenting an outline of our current understanding of the neurobiological basis of fear and anxiety. This outline spans various levels of organization that include the circuitry, molecular pathways, genetic and epigenetic components of fear and anxiety. Using these organizational levels as a scaffold, we then discuss strategies that are currently used to ameliorate these disorders, and forecast future interventions that hold therapeutic promise. Among these newer promising treatments, we include, optogenetic, pharmacological, and extinction-based approaches, as well as lifestyle modifications, with combinatorial treatment regimens of these holding the most promise.
  Current opinion in neurobiology 02/2013; · 7.21 Impact Factor
• Article: Induction of the plasticity-associated immediate early gene Arc by stress and hallucinogens: role of brain-derived neurotrophic factor.

  Madhurima Benekareddy, Amrita R Nair, Brian G Dias, Deepika Suri, Anita E Autry, Lisa M Monteggia, Vidita A Vaidya
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  ABSTRACT: Exposure to stress and hallucinogens in adulthood evokes persistent alterations in neurocircuitry and emotional behaviour. The structural and functional changes induced by stress and hallucinogen exposure are thought to involve transcriptional alterations in specific effector immediate early genes. The immediate early gene, activity regulated cytoskeletal-associated protein (Arc), is important for both activity and experience dependent plasticity. We sought to examine whether trophic factor signalling through brain-derived neurotrophic factor (BDNF) contributes to the neocortical regulation of Arc mRNA in response to distinct stimuli such as immobilization stress and the hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Acute exposure to either immobilization stress or DOI induced Arc mRNA levels within the neocortex. BDNF infusion into the neocortex led to a robust up-regulation of local Arc transcript expression. Further, baseline Arc mRNA expression in the neocortex was significantly decreased in inducible BDNF knockout mice with an adult-onset, forebrain specific BDNF loss. The induction of Arc mRNA levels in response to both acute immobilization stress or a single administration of DOI was significantly attenuated in the inducible BDNF knockout mice. Taken together, our results implicate trophic factor signalling through BDNF in the regulation of cortical Arc mRNA expression, both under baseline conditions and following stress and hallucinogen exposure. These findings suggest the possibility that the regulation of Arc expression via BDNF provides a molecular substrate for the structural and synaptic plasticity observed following stimuli such as stress and hallucinogens.
  The International Journal of Neuropsychopharmacology 03/2012; · 4.58 Impact Factor
• Source

  Available from: Vidita A Vaidya

  Article: Monoaminergic regulation of Sonic hedgehog signaling cascade expression in the adult rat hippocampus.

  Rajeev Rajendran, Shanker Jha, Kimberly A Fernandes, Sunayana B Banerjee, Farhan Mohammad, Brian G Dias, Vidita A Vaidya
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  ABSTRACT: Monoamines are implicated in the modulation of adult hippocampal neurogenesis in depression models and following chronic antidepressant treatment. Given the key role of Sonic hedgehog (Shh) in adult neurogenesis, we examined whether monoaminergic perturbations regulate the expression of Shh or its co-receptors Smoothened (Smo) and Patched (Ptc). Combined depletion of both serotonin and norepinephrine with para-chlorophenylalanine (PCPA) resulted in a significant decrease in Smo and Ptc mRNA within the dentate gyrus subfield of the hippocampus. However, selective depletion of serotonin, using the serotonergic neurotoxin 5,7-dihyrdroxytryptamine (5,7-DHT), or norepinephrine, using the noradrenergic neurotoxin DSP-4, did not alter expression of Shh and its co-receptors, Smo and Ptc. Acute treatment with the monoamine releasing agent, para-chloroamphetamine (PCA) significantly upregulated Smo mRNA within the dentate gyrus. However, acute or chronic treatment with pharmacological antidepressants that modulate monoaminergic neurotransmission did not regulate Shh cascade expression. These results indicate that robust changes in monoamine levels can regulate the expression of the Shh signaling cascade in the adult rodent brain.
  Neuroscience Letters 05/2009; 453(3):190-4. · 2.11 Impact Factor
• Article: Steroidogenic enzyme gene expression in the brain of the parthenogenetic whiptail lizard, Cnemidophorus uniparens.

  Brian George Dias, Sonia Grace Chin, David Crews
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  ABSTRACT: The steroidogenic enzyme CYP17 is responsible for catalyzing the production of androgenic precursors, while CYP19 converts testosterone to estradiol. De novo neurosteroidogenesis in specific brain regions influences steroid hormone dependent behaviors. In the all-female lizard species Cnemidophorus uniparens, individuals alternately display both male-like mounting and female-like receptivity. Mounting is associated with high circulating concentrations of progesterone following ovulation (PostOv), while receptivity is correlated with estrogen preceding it (PreOv). At a neuroanatomical level, the preoptic area (POA) and ventromedial nucleus of the hypothalamus (VMN) are the foci of the male-typical mounting and female-typical receptivity, respectively. In this study, we indirectly test the hypothesis that the whiptail lizard brain is capable of de novo neurosteroidogenesis by cloning fragments of the genes encoding two steroidogenic enzymes, CYP17 and CYP19, and examining their expression patterns in the C. uniparens brain. Our data indicate that these genes are expressed in the C. uniparens brain, and more importantly in the POA and VMN. Using radioactive in situ hybridization, we measured higher CYP17 mRNA levels in the POA of PostOv lizards compared to receptive PreOv animals; CYP19 mRNA levels in the VMN did not change across the ovarian cycle. To our knowledge, these are the first data suggesting that the reptilian brain is capable of de novo steroidogenesis. This study also supports the idea that non-gonadal sources of steroid hormones locally produced in behaviorally relevant brain loci are central to the mediation of behavioral output.
  Brain research 01/2009; 1253:129-38. · 2.46 Impact Factor
• Article: Regulation of pseudosexual behavior in the parthenogenetic whiptail lizard, Cnemidophorus uniparens.

  Brian George Dias, David Crews
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  ABSTRACT: Neuroendocrine mechanisms underlying complementary behaviors like male-typical mounting and female-typical receptivity are most often studied independently in males and females, respectively. Cnemidophorus uniparens is a unisexual lizard species consisting only of females that alternately express male- and female-like pseudosexual behavior across the ovarian cycle. Intact, postovulatory (PostOv), and ovariectomized (OVX), androgen-implanted animals [OVX plus testosterone (T)] exhibit male-like mounting, but not receptivity, whereas intact, preovulatory (PreOv), and OVX lizards injected with estradiol [OVX plus estrogen (E)] express receptivity, but not mounting. We tested whether the serotonergic system in the preoptic area (POA) and ventromedial nucleus of the hypothalamus (VMN) gates the reciprocal inhibition characterizing this alternating expression of mounting and receptivity. Serotonergic signaling at the POA appears to be key to gating male-like behavior. Postovulatory and OVX plus T animals have lower intracellular serotonin (5-HT) levels, and greater abundance of inhibitory 5-HT1A receptor mRNA in the POA compared with both PreOv and OVX plus E lizards. Moreover, injecting 5-HT into the POA of OVX plus T animals suppresses mounting, whereas injection into VMN of OVX plus E lizards suppresses receptivity. Although 5-HT levels in the VMN do not differ across the ovarian cycle or between hormonally manipulated animals, PreOv and OVX plus E lizards have a lower abundance of 5-HT2A mRNA in the VMN. Stimulating 5-HT1A receptors using systemic drug administration inhibits mounting, whereas activating 5-HT2A receptors facilitates receptivity. This study illuminates how male- and female-typical sexual behaviors share common neural circuits, and that 5-HT regulates these naturally complementary, and mutually exclusive, behaviors.
  Endocrinology 06/2008; 149(9):4622-31. · 4.46 Impact Factor