Jyoti Parkash

Central University of Punjab | UCP · Animal Sciences

Alzheimer’s disease (AD) is a complex neurological disorder and multiple pathways are associated with its pathology. Currently available single targeting drugs are found to be ineffective for the treatment of...

Alzheimer's disease (AD) is a multifactorial neurological disorder that affects millions of people worldwide.

MicroRNA (miRNA) are usually 18–25 nucleotides long non-coding RNA targeting post-transcriptional regulation of genes involved in various biological processes. The function of miRNA is essential for maintaining a homeostatic cellular condition, regulating autophagy, cellular motility, and inflammation. Dysregulation of miRNA is responsible for mult...

SNPs could either cause a disorder or directly alter the efficacy of a particular treatment and act as biological markers. The SNP rs7587633 C/T present in the intronic region of the ATG16L1 gene has been studied for its role in psoriasis vulgaris and Palmoplantar pustulosis. To genotype rs7587633 C/T using PCR-RFLP no restriction site is present f...

Ceramide plays an important role in the myelination process; thus, the ceramide biosynthetic pathway could be considered a potential target in managing multiple sclerosis (MS). Fingolimod, an approved drug for MS, is considered a standard modulator of the ceramide biosynthetic pathway in the experimental model of MS. Ursolic acid (UA) exhibited neu...

Background Single Nucleotide Polymorphisms (SNPs) in candidate autophagy gene BECN1 could influence its functions thereby autophagy process. BECN1 noncoding SNPs were found to be significantly associated with neurodegenerative disease and type 2 diabetes mellitus. This study aimed to develop a simultaneous genotyping technique for two BECN1 SNPs (r...

Objective: Genetic background and environmental stimuli play an important role in asthma, which is an individual's hyper-responsiveness to these stimuli leading to airway inflammation. Autophagy Related Gene 5 (ATG5) plays a critical role in the autophagy pathway and has been shown to be involved in asthma. The genetic polymorphisms in the ATG5 hav...

Reactive astrogliosis (RA) is a complex pathological condition where astrocytes undergo specific biochemical changes to attain hypertrophy and hyperplasia. RA is a mechanism being observed in various neurodegenerative disorders (ND) such as Alzheimer's disease (AD), Parkinson's Disease (PD) and traumatic brain Injury (TBI). Various models have been...

Nitric Oxide (NO) is a hetero-nuclear diatomic molecule which is formed from L-arginine through catalytic activity of Nitric Oxide Synthase (NOS). NO is an important messenger molecule known to be involved in dilation of smooth muscles, penile erection, synaptic plasticity. The three isoforms of NOS are nNOS (neuronal NOS), iNOS (inducible NOS), an...

Background Nitric oxide synthase (NOS) is an enzyme that catalyzes the synthesis of nitric oxide (NO) from L-arginine. It has three isoforms: (1) neuronal NOS (nNOS or NOS1), which participates in neural transmission; (2) inducible NOS (iNOS or NOS2), which produces NO in macrophages; and (3) endothelial NOS (eNOS or NOS3) that regulates blood pres...

Autophagy, an intracellular conserved degradative process, plays a central role in the renewal/recycling of a cell to maintain the homeostasis of nutrients and energy within the cell. ATG5, a key component of autophagy, regulates the formation of the autophagosome, a hallmark of autophagy. ATG5 binds with ATG12 and ATG16L1 resulting in E3 like liga...

Alzheimer’s disease (AD) is a progressive degeneration of neurons due to the accumulation of amyloid-β peptide (Aβ) and hyper-phosphorylation of tau protein in the neuronal milieu leading to increased oxidative stress and apoptosis. Numerous factors contribute towards the progression of AD, including miRNA, which are 22–24 nucleotides long sequence...

Highly sophisticated and synchronized interactions of various cells and hormonal signals are required to make organisms competent for reproduction. GnRH neurons act as a common pathway for multiple cues for the onset of puberty and attaining reproductive function. GnRH is not directly receptive to most of the signals required for the GnRH secretion...

A series of morpholine substituted quinazoline derivatives have been synthesized and evaluated for cytotoxic potential against A549, MCF-7 and SHSY-5Y cancer cell lines. These compounds were found to be non-toxic against HEK293 cells at 25 μM and hence display anticancer potential. In these series compounds, AK-3 and AK-10 displayed significant cyt...

Reproduction in mammals is favoured when there is sufficient energy available to permit the survival of offspring. Neuronal nitric oxide synthase expressing neurons produce nitric oxide in the proximity of the gonadotropin-releasing hormone neurons in the preoptic region. nNOS neurons are an integral part of the neuronal network controlling ovarian...

Introduction Nitric oxide (NO) is a diatomic free radical gaseous molecule that is formed from L-arginine through NOS (Nitric oxide synthase) catalyzed reaction. NO controls vascular tone (hence blood pressure), insulin secretion, airway tone, and peristalsis and is involved in angiogenesis (growth of new blood vessels) and in the development of th...

Unlike mammals, two kisspeptins genes encoding, kiss1 and kiss2 are detected in fishes with highly varied and contradictory difference in their reproductive activities. The present study was undertaken to examine the direct action of kisspeptin-10 and its role in gonadal activities in the gonadally quiescent Asian catfish using native mammalian kis...

Alzheimer's disease (AD) is a multifactorial neurological disorder and single target directed drugs have been found ineffective in the retardation or reversal of disease state. In last few years, multi‐targeting agents are being explored as drug strategy for the effective treatment of AD. A series of (4‐(pent‐4‐yn‐1‐yloxy)phenyl)‐2‐phenylpyrimidine...

Hypothalamus being the master regulator of the vertebrate endocrine system undergoes many adjustments/alterations which body makes during the course of aging. Moreover, the endocrinological basis of aging in male and female organisms is very complex, with multiple hormones along the hypothalamic-pituitary (HP) axis interacting with each other via d...

The guidance protein Semaphorin7A (Sema7A) is required for the proper development of the immune and nervous systems. Despite strong expression in the mature brain, the role of Sema7A in the adult remains poorly defined. Here we show that Sema7A utilizes different cell surface receptors to control the proliferation and differentiation of neural prog...

Supplementary Figures 1-10 and Supplementary Tables 1-2

A sparse population of a few hundred primarily hypothalamic neurons forms the hub of a complex neuroglial network that controls reproduction in mammals by secreting the 'master molecule' gonadotropin-releasing hormone (GnRH). Timely postnatal changes in GnRH expression are essential for puberty and adult fertility. Here we report that a multilayere...

Supplementary tables.

The linkage disequilibrium table representing important SNPs.

Autophagy is an essential, homeostatic process which removes damaged cellular proteins and organelles for cellular renewal. ATG5, a part of E3 ubiquitin ligase-like complex (Atg12-Atg5/Atg16L1), is a key regulator involved in autophagosome formation - a crucial phase of autophagy. In this study, we used different in silico methods for comprehensive...

A sparse population of a few hundred primarily hypothalamic neurons forms the hub of a complex neuroglial network that controls reproduction in mammals by secreting the 'master molecule' gonadotropin-releasing hormone (GnRH). Timely postnatal changes in GnRH expression are essential for puberty and adult fertility. Here we report that a multilayere...

Anti-Müllerian hormone (AMH) plays crucial roles in sexual differentiation and gonadal functions. However, the possible extragonadal effects of AMH on the hypothalamic-pituitary-gonadal axis remain unexplored. Here we demonstrate that a significant subset of GnRH neurons both in mice and humans express the AMH receptor, and that AMH potently activa...

Reproductive competence in mammals depends on the projection of gonadotropin-releasing hormone (GnRH) neurons to the hypothalamic median eminence (ME) and the timely release of GnRH into the hypothalamic-pituitary-gonadal axis. In adult rodents, GnRH neurons and the specialized glial cells named tanycytes periodically undergo cytoskeletal plasticit...

Excess nutrient supply and rapid weight gain during early life are risk factors for the development of obesity during adulthood. This metabolic malprogramming may be mediated by endocrine disturbances during critical periods of development. Ghrelin is a metabolic hormone secreted from the stomach that acts centrally to promote feeding behavior by b...

The transition to puberty and adult fertility both require a minimum level of energy availability. The adipo-cyte-derived hormone leptin signals the long-term status of peripheral energy stores and serves as a key metabolic messenger to the neuroendocrine reproductive axis. Humans and mice lacking leptin or its receptor fail to complete puberty and...

The transition to puberty and adult fertility both require a minimum level of energy availability. The adipocyte-derived hormone leptin signals the long-term status of peripheral energy stores and serves as a key metabolic messenger to the neuroendocrine reproductive axis. Humans and mice lacking leptin or its receptor fail to complete puberty and...

Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neur...

Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neur...

Reproduction in mammals is dependent on the function of hypothalamic neurons whose axons project to the hypothalamic median eminence (ME) where they release gonadotropin-releasing hormone (GnRH) into a specialized capillary network for delivery to the anterior pituitary. These neurons originate prenatally in the nasal placode and migrate into the f...

The anti-neuropilin1 (Nrp1) polyclonal antibody AF566 (R & D systems) selectively recognizes the semaphorin-binding domain of the protein. Top panel: western blot analysis of Nrp1 in protein extracts from the hypothalamus of Nrp1+/+, Nrp1sema/+ and Nrp1sema/sema mice (antibody used at 1∶1000 dilution). Bottom panel: immunohistofluorescence analysis...

GnRH cell migration is not affected in GnRH::cre; Nrp1loxP/loxP conditional knockout mice that lack Nrp1 only in GnRH cells. (A) Immunohistofluorescence analysis of the frontonasal region (sagittal sections, single plane confocal microscopy images) in Nrp1loxP/loxP and GnRH::cre; Nrp1loxP/loxP mice at E14.5, with anti-GnRH (green) and anti-Nrp1 (re...

NRP1 sequencing primers. (DOCX)

Many GnRH cells migrate along ectopic nerve fibers in the brain of Nrp1sema/sema mutant mice. Immunohistofluorescence analysis of sagittal sections of the rostral and ventral forebrain regions in Nrp1+/+ and Nrp1sema/sema mice at E14.5, with anti-GnRH (green) and anti-peripherin (red) antibodies. Insets show detailed views of the normal and the abe...

SEMA3A sequencing primers. (DOCX)

Kallmann syndrome (KS) associates congenital hypogonadism due to gonadotropin-releasing hormone (GnRH) deficiency and anosmia. The genetics of KS involves various modes of transmission, including oligogenic inheritance. Here, we report that Nrp1(sema/sema) mutant mice that lack a functional semaphorin-binding domain in neuropilin-1, an obligatory c...

Reproduction is controlled in the brain by a neural network that drives the secretion of gonadotropin-releasing hormone (GnRH). Various permissive homeostatic signals must be integrated to achieve ovulation in mammals. However, the neural events controlling the timely activation of GnRH neurons are not completely understood. Here we show that kissp...

Dieldrin is an endocrine disruptor that accumulates in mammalian adipose tissue and brain. It induces convulsions due to its antagonism of the γ-aminobutyric acid A receptor (GABA(A)R). We have previously reported that long-term exposure to dieldrin causes the internalization of the N-methyl-D-aspartate receptor (NMDAR) as a result of persistent GA...

Reproduction in mammals is dependent on the function of specific neurons that secrete gonadotropin-releasing hormone-1 (GnRH-1). These neurons project to the median eminence of the hypothalamus where GnRH-1 is released into the pituitary portal blood for delivery to the anterior pituitary, eliciting the secretion of luteinizing hormone and follicle...

Reproduction in mammals, including humans, requires adequate energy availability to enter into puberty and for ongoing fertility during adulthood. Leptin, an adipocyte-derived hormone, provides information about peripheral energy stores to the central reproductive axis, yet its site(s) of action remain unclear. Mapping of the leptin receptor (LepRb...

There is abundant evidence to prove that the astrocytes are highly dynamic cell type in CNS and under physiological conditions such as reproduction, these cells display a remarkable structural plasticity especially at the level of their distal processes ensheathing the gonadotropin releasing hormone (GnRH) axon terminals. The morphology of GnRH axo...

Nitric oxide (NO) is a peculiar chemical transmitter that freely diffuses through aqueous and lipid environments and plays a role in major aspects of brain function. Within the hypothalamus, NO exerts critical effects upon the gonadotropin-releasing hormone (GnRH) network to maintain fertility. Here, we review recent evidence that NO regulates majo...

Although coordinated actions of several areas within the hypothalamus are involved in the secretion of gonadotrophin-releasing hormone (GnRH), the median eminence of the hypothalamus, where the nerve terminals are located, plays a particularly critical role in the release of GnRH. In adult females, prior to the preovulatory surge of GnRH, the retra...

P207-005 Estradiol counteracts NMDAR internalization induced by long-term exposure to dieldrin in cortical neurons V. Briz 1, M. Galofré 1, J. Parkash2, V. Prevot2, C. Suñol1 1 Institut d’Investigacions Biomediques de Barcelona, CSIC-ISIBAPS, CIBERESP, Spain, 2 Inserm U837, Jean-Pierre Aubert Research Center, Lille Cedex, France. Dieldrin is a...

As the final common pathway for the central control of gonadotropin secretion, GnRH neurons are subjected to numerous regulatory homeostatic and external factors to achieve levels of fertility appropriate to the organism. The GnRH system thus provides an excellent model in which to investigate the complex relationships between neurosecretion, morph...

Within the preoptic region, nitric oxide (NO) production varies during the ovarian cycle and has the ability to impact hypothalamic reproductive function. One mechanism for the regulation of NO release mediated by estrogens during the estrous cycle includes physical association of the calcium-activated neuronal NO synthase (nNOS) enzyme with the gl...

In rodents, the cell bodies of gonadotrophin- releasing hormone (GnRH) neurones are diffusely distributed in the preoptic region of the hypothalamus. The aim of this study was to examine the effect of estradiol on the neuroanatomical relationship between GnRH neurons and polysialylated form of neural cell adhesion molecule (PSA-NCAM) a known marker...

In rodents, the cell bodies of gonadotrophin- releasing hormone (GnRH) neurones are diffusely distributed in the preoptic region of the hypothalamus. The aim of this study was to examine the effect of estradiol on the neuroanatomical relationship between GnRH neurons and polysialylated form of neural cell adhesion molecule (PSA-NCAM) a known marker...

Dietary restriction (DR) is known to have potential health benefits including enhanced resistance of neurons to excitotoxic, oxidative and metabolic insults, cancer, stress, diabetes, reduced morbidity, and increased life span. In the present study, we examined the effect of DR (alternate day feeding regimen) on neurogenesis, expression of immature...

Gonadotropin releasing hormone (GnRH)-secreting neurons in mammal's project principally to the median eminence-arcuate (ME-ARC) region where they make contact with basal lamina and open into the pericapillary space of the primary hypophyseal portal plexus. In the present study we report the expression of polysialylated form of neural cell adhesion...

The present study was designed to establish the dynamic regulation of polysialylated form of neural cell adhesion molecule (PSA-NCAM) expression by neurotransmitters controlling gonadotropin releasing hormone (GnRH) secretion. The expression of PSA-NCAM and glial fibrillary acidic protein (GFAP) on GnRH cell bodies and axon terminals in the medial...

The gonadotropin-releasing hormone (GnRH) neurosecretory system undergoes marked structural and functional changes during the ovarian cycle. The aim of this study was to examine the neuroanatomical relationship between GnRH neurons and a polysialylated form of neural cell adhesion molecule (PSA-NCAM), a known marker of neuronal plasticity. Using im...