Neuropeptides

Editorial Board

2012-02-01

Vascular endothelial growth factor (VEGF) and its role in the central nervous system: A new element in the neurotrophic hypothesis of antidepressant drug action

Marta Maria Nowacka, Ewa Obuchowicz — 2011-06-30

Abstract: Vascular endothelial growth factor (VEGF) is a well-known cellular mitogen, and a vascular growth factor and permeability regulator. It participates in physiological and pathological processes of angiogenesis and in the development of lymphatic vessels. In addition to the proangiogenic activity, studies of recent years have revealed neurotrophic and neuroprotective potential of VEGF both in the peripheral and central nervous system. VEGF directly influences Schwann cells, neuronal progenitor cells, astrocytes and microglia. This factor plays an import role in developmental processes of the nervous tissue since it is implicated in neurogenesis and the regulation of neuronal development, and in the differentiation and formation of vessels in the brain. VEGF elicits its biological effect via an interaction with three VEGF receptor subtypes: VEGFR1, VEGFR2 and VEGFR3. In the nervous system, VEGFR2 signaling prevails. VEGF as a trophic factor, influencing both vascular endothelial cells and brain cells is a focus of the studies on neuropsychiatric disorders and psychotropic drug action. Antidepressant drugs were shown to induce hippocampal expression of VEGF. In addition, the experiments in animals models of depression have demonstrated that VEGFR2 signaling is indispensable for cellular and behavioral response to antidepressant drugs. Acquiring a deeper knowledge into the signaling pathways engaged in neurogenic and behavioral VEGF actions can unravel new targets for more efficient and quick acting antidepressant drugs.

The effect of pituitary adenylate cyclase-activating polypeptide on elevated plus maze behavior and hypothermia induced by morphine withdrawal

2012-01-09

Abstract: The aim of the present investigation was to study the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on morphine withdrawal-induced behavioral changes and hypothermia in male CFLP mice. Elevated plus maze (EPM) and jump tests were used to assess naloxone-precipitated morphine withdrawal-induced behavior responses. Different doses of subcutaneous (s.c.) naloxone, (0.1 and 0.2mg/kg, respectively) were used to precipitate the emotional and psychical aspects of withdrawal on EPM and 1mg/kg (s.c.) was used to induce the somatic withdrawal signs such as jumping, and the changes in body temperature. In our EPM studies, naloxone proved to be anxiolytic in mice treated with morphine. Chronic intracerebroventricular (i.c.v.) administration of PACAP alone had no significant effect on withdrawal-induced anxiolysis and total activity at doses of 500ng and 1μg. At dose of 500ng, however, PACAP significantly counteracted the reduced motor activity in the EPM test in mice treated with morphine and diminished the hypothermia and shortened jump latency induced by naloxone in mice treated with morphine.These findings indicate that anxiolytic-like behavior may be mediated via a PACAP-involved pathway and PACAP may play an important role in chronic morphine withdrawal-induced hypothermia as well.

Changes in galanin and GalR1 gene expression in discrete brain regions after transient occlusion of the middle cerebral artery in female rats

2011-12-26

Abstract: Injury to neurons results in up-regulation of galanin in some central and peripheral systems, and it has been suggested that this neuropeptide may play a protective and trophic role, primarily mediated by galanin receptor 2 (GalR2). The objective of the present study was to investigate galanin, GalR1, GalR2 and GalR3 gene expression in the female rat brain 7days after a 60-min unilateral occlusion of the middle cerebral artery followed by reperfusion. Quantitative real-time PCR was employed in punch-biopsies from the locus coeruleus, somatosensory cortex and dorsal hippocampal formation, including sham-operated rats as controls. Galanin gene expression showed a ∼2.5-fold increase and GalR1 a ∼1.5-fold increase in the locus coeruleus of the ischemic hemisphere compared to the control side. Furthermore, the GalR1 mRNA levels decreased by 35% in somatosensory cortex of the ischemic hemisphere. Immunohistochemical analysis indicated a depletion of galanin from cell bodies and dendrites in the locus coeruleus after middle cerebral artery occlusion. The present results suggest that a stroke-induced forebrain lesion up-regulates synthesis of galanin and GalR1 in the locus coeruleus, a noradrenergic cell group projecting to many forebrain areas, including cortex and the hippocampal formation. These results support the notion that galanin may play a role in the response of the central nervous system to injury.

Altered expression of neuropeptides in the primary somatosensory cortex of the Down syndrome model Ts65Dn

2011-11-14

Abstract: Down syndrome is the most common genetic disorder associated with mental retardation. Subjects and mice models for Down syndrome (such as Ts65Dn) show defects in the formation of neuronal networks in both the hippocampus and the cerebral cortex. The principal neurons display alterations in the morphology, density and distribution of dendritic spines in the cortex as well as in the hippocampus. Several evidences point to the possibility that the atrophy observed in principal neurons could be mediated by changes in their inhibitory inputs and, in fact, an imbalance between excitation and inhibition has been observed in Ts65Dn mice in these regions, which are crucial for learning and information processing. These animals have an increased density of interneurons in the primary somatosensory cortex, especially of those expressing calretinin and calbindin D-28k. Here, we have analysed the expression and distribution of several neuropeptides in the primary somatosensory cortex of Ts65Dn mice in order to investigate whether these subpopulations of interneurons are affected. We have observed an increase in the total density of somatostatin expressing interneurons and of those expressing VIP in layer IV in Ts65Dn mice. The typology of the somatostatin and VIP interneurons was unaltered as attested by the pattern of co-expression with other markers. Somatostatin immunoreactive neurons co-express mainly D-28k calbindin and VIP expressing interneurons maintain its pattern of co-expression with calcium binding proteins. These alterations, in case they were also present in subjects with Down syndrome, could be related to their impairment in cognitive profile and could be involved in the neurological defects observed in this disorder.

Endogenous opioid peptide-mediated neurotransmission in central and pericentral nuclei of the inferior colliculus recruits μ1-opioid receptor to modulate post-ictal antinociception

Tatiana Tocchini Felippotti, Renato Leonardo de Freitas, Norberto Cysne Coimbra — 2011-11-21

Abstract: Background: The aim of the present work was to investigate the involvement of the μ1-endogenous opioid peptide receptor-mediated system in post-ictal antinociception.Methods: Antinociceptive responses were determined by the tail-flick test after pre-treatment with the selective μ1-opioid receptor antagonist naloxonazine, peripherally or centrally administered at different doses.Results: Peripheral subchronic (24h) pre-treatment with naloxonazine antagonised the antinociception elicited by tonic–clonic seizures. Acute (10min) pre-treatment, however, did not have the same effect. In addition, microinjections of naloxonazine into the central, dorsal cortical and external cortical nuclei of the inferior colliculus antagonised tonic–clonic seizure-induced antinociception. Neither acute (10-min) peripheral pre-treatment with naloxonazine nor subchronic intramesencephalic blockade of μ1-opioid receptors resulted in consistent statistically significant differences in the severity of tonic–clonic seizures shown by , although the intracollicular specific antagonism of μ1-opioid receptor decreased the duration of seizures.Conclusion: μ1-Opioid receptors and the inferior colliculus have been implicated in several endogenous opioid peptide-mediated responses such as antinociception and convulsion. The present findings suggest the involvement of μ1-opiate receptors of central and pericentral nuclei of the inferior colliculus in the modulation of tonic–clonic seizures and in the organisation of post-ictal antinociception.

The nitric oxide pathway participates in lordosis behavior induced by central administration of leptin

2011-10-24

Abstract: Intracerebroventricular (icv) administration of leptin facilitates lordosis behavior in ad libitum-fed, estrogen-primed rats. The cellular mechanism involved in this response is unknown. The present study tested the hypothesis that the nitric oxide-guanylyl cyclase, cGMP-dependent protein kinase (PKG) pathway is involved in the facilitation of lordosis behavior induced by the central administration of leptin. We tested the importance of the nitric oxide/cGMP pathway for lordosis stimulation by either icv infusion of a nitric oxide synthase inhibitor (L-NAME) or a nitric oxide-dependent, soluble guanylyl cyclase inhibitor (ODQ) 30min before leptin administration (1μg). This dose of leptin reliably induced lordosis behavior in ovariectomized estradiol benzoate treated rats. The lordosis induced by leptin at 1 and 2h after infusion was significantly reduced by the previous injection of either L-NAME or by ODQ. Intracerebroventricular infusion of the PKG inhibitor (KT5823) 30min before leptin infusion, also significantly inhibited the lordosis behavior induced by leptin at 1 and 2h after hormone administration. These data support the hypothesis that the nitric oxide/cGMP/PKG pathway is involved in the facilitation of lordosis by leptin in estrogen-primed female rats.

Neurochemical classification and projection targets of CART peptide immunoreactive neurons in sensory and parasympathetic ganglia of the head

Jason J. Ivanusic, Kate E. Goulding, Matthew M.K. Kwok, Ernest A. Jennings — 2011-10-17

Abstract: The aims of the present study were to determine if there is neuronal Cocaine and amphetamine regulated transcripts (CART) peptide expression (CART+) in parasympathetic (sphenopalatine (SPG); otic (OG)) and sensory (trigeminal (TG)) ganglia of the head and to examine the neurochemical phenotype (calcitonin gene-related peptide (CGRP), neurofilament 200 (NF200), isolectin B4 (IB4) binding, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and enkephalin (ENK) immunoreactivity) and projection targets (lacrimal gland (LG), parotid gland (PG), nasal mucosa (NM), temporomandibular joint (TMJ), middle cerebral artery (MCA) and middle meningeal artery (MMA)) of CART expressing neurons in these ganglia. We found CART+ neurons in both the SPG (5.25±0.07%) and OG (4.32±0.66). A significant proportion of these CART+ neurons contained VIP, NPY or ENK (34%, 26% and 11%, respectively). SPG neurons retrogradely labelled from the lacrimal gland (29%) were CART+, but we were unable to demonstrate CART+ labelling in any of the SPG or OG neurons labelled from other targets. This supports a role for CART peptides in lacrimation or regulation of vascular tone in the lacrimal gland, but not in salivation or nasal congestion. CART+ neurons were also present in the trigeminal ganglion (1.26±0.38%), where their size distribution was confined almost completely to neurons smaller than 800 μm2 (mean=410μm2; 98%<800μm2), and were almost always CGRP+, but did not bind IB4. This is consistent with a role for CART peptides in trigeminal pain. However, there were few CART+ neurons amongst any of the trigeminal neurons retrogradely labelled from the targets we investigated and thus we cannot comment on the tissue type where such pain may have originated. Our study shows that some specialization of CART peptide expression (based on neurochemical phenotype and target projection) is evident in sensory and parasympathetic ganglia of the head.

Meetings Calendar

2012-02-01