Neuropeptides in the rat claustrum - An immunohistochemical detection.

Neuropeptides are involved in numerous brain activities and are responsible for a wide spectrum of higher mental functions. The main purpose of this outline structural qualitative study was to identify the possible immunoreactivity of classical neuropeptides, as well as novel ones such as nesfatin-1, phoenixin (PNX), spexin (SPX), neuromedin U (NMU) and respective receptors within the rat claustrum for the first time. The study shows the novel identification of peptidergic neurotransmission in the rat claustrum which potentially implicates a contribution of this neuropeptide to numerous central neurosecretory mechanisms.

Spexin and nesfatin-1-expressing neurons in the male human claustrum.

Neuropeptides are involved in numerous brain activities being responsible for a wide spectrum of higher mental functions. The purpose of this concise, structural and qualitative investigation was to map the possible immunoreactivity of the novel regulatory peptides: spexin (SPX) and nesfatin-1 within the human claustrum. SPX is a newly identified peptide, a natural ligand for the galanin receptors (GALR) 2/3, with no molecular structure similarities to currently known regulatory factors. SPX seems to have multiple physiological functions, with an involvement in reproduction and food-intake regulation recently revealed in animal studies. Nesfatin-1, a second pleiotropic neuropeptide, which is a derivative of the nucleobindin-2 (NUCB-2) protein, is characterized by a wide distribution in the brain. Nesfatin-1 is a substance with a strong anorexigenic effect, playing an important role in the neuronal circuits of the hypothalamus that regulate food intake and energy homeostasis. On the other hand, nesfatin-1 may be involved in several important brain functions such as sleep, reproductive behaviour, cognitive processes, stress responses and anxiety. For the first time we detected and described a population of nesfatin-1 and SPX expressing neurons in the human claustrum using immunohistochemical and fluorescent methods. The study presents the novel identification of SPX and nesfatin-1 immunopositive neurons in the human claustrum and their assemblies show similar patterns of distribution in the whole structure.

Modulatory effect of olanzapine on neuronal nitric oxide synthase (nNOS) expression in the rat striatum.

Nitric oxide (NO) has been thought to be a novel factor involved in the mechanisms of mental disorders pathogenesis for quite some time. However, little is known about potential crosstalk between neuronal NO signaling and neuroleptics action. The present work was, therefore, focused on gene expression of neuronal NO synthase (nNOS) in the brains of rats chronically treated with olanzapine, an atypical antipsychotic drug. Studies were carried out on adult, male Sprague-Dawley rats that were divided into 2 groups: control and experimental animals treated with olanzapine (28-day-long intraperitoneal injection, at dose 5 mg/kg daily). All individuals were killed under anesthesia and the whole brains excised. Immunohistochemical procedure was used for histological assessment of the whole brain, and for both descriptive and quantitative analysis of nNOS protein distribution in selected brain structures. Long-term treatment with olanzapine is reflected in different changes in the number of enzyme-expressing cells in the rat brain. Olanzapine decreased the number of nNOS-expressing cells and possibly reduced NO synthesis in the rat striatum. Olanzapine can be taken into account as a potential inhibitor of NO synthesis in the rat striatum.

Olanzapine alters the expression of gasotransmitter-related enzymes: CBS and HO-2 in the rat hippocampus and striatum.

BACKGROUND: Gaseous neurotransmitters have been thought to be novel factors involved in the mechanisms of mental disorders pathogenesis for quite some time. However, little is known about the potential crosstalk between neuronal gasotransmitter signaling and neuroleptics action. The present work was, therefore, focused on gene expression of H2S and CO-producing enzymes in the brains of rats chronically treated with olanzapine, an atypical antipsychotic drug. METHODS: Studies were carried out on adult, male Sprague-Dawley rats that were divided into 2 groups: control and experimental animals treated with olanzapine (28-day-long intraperitoneal injection, at a dose of 5 mg/kg daily). All individuals were sacrificed under anesthesia and the whole brains excised. Immunohistochemical procedure was used for histological assessment of the whole brain and for quantitative analysis of cystathionine ß-synthase (CBS) and heme oxygenase 2 (HO-2) protein distribution in selected brain structures. RESULTS: Long-term treatment with olanzapine is reflected in different changes in the number of enzymes-expressing cells in the rat brain. Olanzapine decreased the number of CBS-expressing cells and possibly reduced H2S synthesis in the hippocampus and striatum. The antipsychotic administration increased the number of HO-2 immunopositive cells and probably stimulated the CO production in the hippocampus. CONCLUSIONS: Modulatory effect of olanzapine on cellular mechanisms of gasotransmitter synthesis may be an alternative way of their pharmacological action.

The smell of death. State-of-the-art and future research directions.

The decomposition of a body is inseparably associated with the release of several types of odors. This phenomenon has been used in the training of sniffer dogs for decades. The odor profile associated with decomposition consists of a range of volatile organic compounds (VOCs), chemical composition of which varies over time, temperature, environmental conditions, and the type of microorganisms, and insects colonizing the carcass. Mercaptans are responsible for the bad smell associated with corpses; however, there are no unified recommendations for conducting forensic analysis based on the detectable odor of revealed corpses and previous research on VOCs shows differing results. The aim of this review is to systematize the current knowledge on the type of volatile organic compounds related to the decomposition process, depending on a few variables. This knowledge will improve the methods of VOCs detection and analysis to be used in modern forensic diagnostics and improve the methods of training dogs for forensic applications.

Pharmacomodulation of brain neuromedin U signaling as a potential therapeutic strategy.

Neuromedin U (NMU) belongs to a family of multifunctional neuropeptides that modulate the activity of several neural networks of the brain. Acting via metabotropic receptor NMUR2, NMU plays a role in the regulation of multiple systems, including energy homeostasis, stress responses, circadian rhythms, and endocrine signaling. The involvement of NMU signaling in the central regulation of important neurophysiological processes and its disturbances is a potential target for pharmacological modulation. Number of preclinical studies have proven that both modified NMU analogues such as PASR8-NMU or F4R8-NMU and designed NMUR2 agonists, for example, CPN-116, CPN-124 exhibit a distinct pharmacological activity especially when delivered transnasally. Their application can potentially be useful in the more convenient and safe treatment of obesity, eating disorders, Alzheimer's disease-related memory impairment, alcohol addiction, and sleep disturbances. Accumulating findings suggest that pharmacomodulation of the central NMU signaling may be a promising strategy in the treatment of several neuropsychiatric disorders.

Amantadine in Treatment of Dysthymia-The Pilot Case Series Study.

Dysthymia is a common chronic mood disorder in which isolated symptoms of depression persist for at least 2 years. Despite the many medications recommended for the treatment of dysthymia, no recommendations have yet been made for the treatment of patients who fail to achieve clinical improvement. This justifies attempts to identify second-line drugs for the treatment of dysthymia. In an open and naturalistic case study, five patients diagnosed with dysthymia in whom at least one antidepressant treatment was ineffective were treated with amantadine. In the age- and gender-matched external control group, patients were treated with sertraline at 100 mg/day. Depressive symptoms were assessed using HDRS-17. Two men and three women were treated with 100 mg amantadine for 3 months with 3-5 months follow-up. After 1 month of treatment with amantadine, a significant reduction in the intensity of depressive symptoms was achieved in all patients, and the clinical improvement increased over the next 2 months of treatment. No deterioration in well-being was observed in any patient after discontinuation of amantadine. The effect of amantadine treatment was comparable to that of sertraline treatment in patients with dysthymia who improved with this drug. The present study indicates that amantadine is an effective and well-tolerated drug in the treatment of dysthymia. Amantadine may be associated with a quick improvement in symptoms in the treatment of dysthymia. Treatment with this drug seems to be associated with good tolerability and persistency of the therapeutic effect after the discontinuation of the treatment.

Evaluation of Peripheral Blood Concentrations of Phoenixin, Spexin, Nesfatin-1 and Kisspeptin as Potential Biomarkers of Bipolar Disorder in the Pediatric Population.

There are some initial suggestions in the literature that phoenixin, spexin, nesfatin-1 and kisspeptin may play a role in the pathogenesis of affective disorders. Therefore, they may also be cautiously considered as potential diagnostic or predictive biomarkers of BD. This study aimed to evaluate the levels of the aforementioned neuropeptides in the peripheral blood of children and adolescents with bipolar. This study included 122 individuals: 67 persons with diagnosed bipolar disorder types I and II constituted the study group, and 55 healthy persons were included in the control group. Statistically significant differences in the concentrations of neuropeptides between the control and study groups were noted in relation to nesfatin-1 and spexin (although spexin lost statistical significance after introducing the Bonferroni correction). In a logistic regression analysis, an increased risk of bipolar disorder was noted for a decrease in nesfatin-1 concentration. Lower levels of nesfatin-1 seemed to be a significant risk factor for the development of bipolar disorder types I and II. Furthermore, the occurrence of bipolar disorder was associated with significantly elevated levels of spexin. None of the analyzed neuropeptides was significantly correlated with the number of symptoms of bipolar disorder.

Chronic treatment with escitalopram and venlafaxine affects the neuropeptide S pathway differently in adult Wistar rats exposed to maternal separation.

Neuropeptide S (NPS), which is a peptide that is involved in the regulation of the stress response, seems to be relevant to the mechanism of action of antidepressants that have anxiolytic properties. However, to date, there have been no reports regarding the effect of long-term treatment with escitalopram or venlafaxine on the NPS system under stress conditions. This study aimed to investigate the effects of the above-mentioned antidepressants on the NPS system in adult male Wistar rats that were exposed to neonatal maternal separation (MS). Animals were exposed to MS for 360 min. on postnatal days (PNDs) 2-15. MS causes long-lasting behavioral, endocrine and neurochemical consequences that mimic anxiety- and depression-related features. MS and non-stressed rats were given escitalopram or venlafaxine (10mg/kg) IP from PND 69 to 89. The NPS system was analyzed in the brainstem, hypothalamus, amygdala and anterior olfactory nucleus using quantitative RT-PCR and immunohistochemical methods. The NPS system was vulnerable to MS in the brainstem and amygdala. In the brainstem, escitalopram down-regulated NPS and NPS mRNA in the MS rats and induced a tendency to reduce the number of NPS-positive cells in the peri-locus coeruleus. In the MS rats, venlafaxine insignificantly decreased the NPSR mRNA levels in the amygdala and a number of NPSR cells in the basolateral amygdala, and increased the NPS mRNA levels in the hypothalamus. Our data show that the studied antidepressants affect the NPS system differently and preliminarily suggest that the NPS system might partially mediate the pharmacological effects that are induced by these drugs.

The intervertebral discs' fibrocartilage as a DNA source for genetic identification in severely charred cadavers.

Identifying charred human remains poses a challenge to forensic laboratories. High temperature completely incinerates the superficial tissues and partially destroys bones, forcing the forensics to seek an alternative, for bones and teeth, forensic material that should quickly and cheaply deliver DNA of sufficient quantity and quality. We sought, other than rib cartilage, types of cartilages that could serve as a DNA source. DNA was isolated from the fibrous cartilage of a fibrous ring of intervertebral L1-L2 discs sampled from charred cadavers or charred body fragments: 5 victims of car fires, 1 victim of combustion during a residential house gas explosion, and 3 victims of nitroglycerin explosion. DNA was isolated by the column method. DNA quality and concentration were assessed by RT-PCR and multiplex PCR for 23 autosomal and 17 Y chromosome STR loci. STR polymorphism results obtained by capillary electrophoresis served for likelihood ratio (LR) calculations. DNA concentration in relation to the cadaver's age and post-mortem interval (PMI) were analyzed. All samples (n = 9) yielded good-quality DNA in quantities (0.57-17.51 ng/µL for T. Large autosomal sequence) suitable for STR-based amplification. The isolated DNA characterized a low degradation index (0.80-1.99), and we were able to obtain complete genetic profiles. In each of the nine cases, the genotyping results allowed identifying the victims based on comparative material from the immediate family. The results demonstrate the usefulness of human intervertebral disc fibrocartilage as an alternative DNA source for the genetic identification of charred bodies or charred torso fragments.

Modulatory effect of long-term treatment with escitalopram and clonazepam on the expression of anxiety-related neuropeptides: neuromedin U, neuropeptide S and their receptors in the rat brain.

BACKGROUND: Newly identified multifunctional peptidergic modulators of stress responses: neuromedin U (NMU) and neuropeptide S (NPS) are involved in the wide spectrum of brain functions. However, there are no reports dealing with potential molecular relationships between the action of diverse anxiolytic or antidepressant drugs and NMU and NPS signaling in the brain. The present work was therefore focused on local expression of the aforementioned stress-related neuropeptides in the rat brain after long-term treatment with escitalopram and clonazepam. METHODS: Studies were carried out on adult, male Sprague-Dawley rats that were divided into 3 groups: animals injected with saline (control) and experimental individuals treated with escitalopram (at single dose 5 mg/kg daily), and clonazepam (at single dose 0.5 mg/kg). All individuals were sacrificed under anaesthesia and the whole brain excised. Total mRNA was isolated from homogenized samples of amygdala, hippocampus, hypothalamus, thalamus, cerebellum and brainstem. Real time-PCR method was used for estimation of related NPS, NPS receptor (NPSR), NMU, NMU and receptor 2 (NMUR2) mRNA expression. The whole brains were also sliced for general immunohistochemical assessment of the neuropeptides expression. RESULTS: Chronic administration of clonazepam resulted in an increase of NMU mRNA expression and formation of NMU-expressing fibers in the amygdala, while escitalopram produced a significant decrease in NPSR mRNA level in hypothalamus. Long-term escitalopram administration affects the local expression of examined neuropeptides mRNA in a varied manner depending on the brain structure. CONCLUSIONS: Pharmacological effects of escitalopram may be connected with local at least partially NPSR-related alterations in the NPS/NMU/NMUR2 gene expression at the level selected rat brain regions. A novel alternative mode of SSRI action can be therefore cautiously proposed.

Escitalopram alters local expression of noncanonical stress-related neuropeptides in the rat brain via NPS receptor signaling.

BACKGROUND: Neuropeptide S (NPS) is a multifunctional regulatory factor that exhibits a potent anxiolytic activity in animal models. However, there are no reports dealing with the potential molecular relationships between the anxiolytic activity of selective serotonin reuptake inhibitors (SSRIs) and NPS signaling, especially in the context of novel stress-related neuropeptides action. The present work therefore focused on gene expression of novel stress neuropeptides in the rat brain after acute treatment with escitalopram and in combination with neuropeptide S receptor (NPSR) blockade. METHODS: Studies were carried out on adult, male Sprague-Dawley rats that were divided into five groups: animals injected with saline (control) and experimental rats treated with escitalopram (at single dose 10 mg/kg daily), escitalopram and SHA-68, a selective NPSR antagonist (at a single dose of 40 mg/kg), SHA-68 alone and corresponding vehicle (solvent SHA-68) control. To measure anxiety-like behavior and locomotor activity the open field test was performed. All individuals were killed under anaesthesia and the whole brain was excised. Total mRNA was isolated from homogenized samples of the amygdala, hippocampus, hypothalamus, thalamus, cerebellum, and brainstem. Real-time PCR was used for estimation of related NPS, NPSR, neuromedin U (NMU), NMU receptor 2 (NMUR2) and nesfatin-1 precursor nucleobindin-2 (NUCB2) gene expression. RESULTS: Acute escitalopram administration affects the local expression of the examined neuropeptides mRNA in a varied manner depending on brain location. An increase in NPSR and NUCB2 mRNA expression in the hypothalamus and brainstem was abolished by SHA-68 coadministration, while NMU mRNA expression was upregulated after NPSR blockade in the hippocampus and cerebellum. CONCLUSIONS: The pharmacological effects of escitalopram may be connected with local NPSR-related alterations in NPS/NMU/NMUR2 and nesfatin-1 gene expression at the level of selected rat brain regions. A novel alternative mode of SSRI action can be therefore cautiously proposed.

Effect of Escitalopram on the Number of DCX-Positive Cells and NMUR2 Receptor Expression in the Rat Hippocampus under the Condition of NPSR Receptor Blockade.

BACKGROUND: Neuropeptide S (NPS) is a multifunctional regulatory factor that exhibits a potent anxiolytic activity in animal models. However, there are no reports dealing with the potential molecular interactions between the activity of selective serotonin reuptake inhibitors (SSRIs) and NPS signaling, especially in the context of adult neurogenesis and the expression of noncanonical stress-related neuropeptides such as neuromedin U (NMU). The present work therefore focused on immunoexpression of neuromedin U receptor 2 (NMUR2) and doublecortin (DCX) in the rat hippocampus after acute treatment with escitalopram and in combination with selective neuropeptide S receptor (NPSR) blockade. METHODS: Studies were carried out on adult, male Sprague-Dawley rats that were divided into five groups: animals injected with saline (control) and experimental individuals treated with escitalopram (at single dose 10 mg/kg daily), escitalopram + SHA-68, a selective NPSR antagonist (at single dose 40 mg/kg), SHA-68 alone, and corresponding vehicle control. All animals were sacrificed under halothane anaesthesia. The whole hippocampi were quickly excised, fixed, and finally sliced for general qualitative immunohistochemical assessment of the NPSR and NMUR2 expression. The number of immature neurons was enumerated using immunofluorescent detection of doublecortin (DCX) expression within the subgranular zone (SGZ). RESULTS: Acute escitalopram administration affects the number of DCX and NMUR2-expressing cells in the adult rat hippocampus. A decreased number of DCX-expressing neuroblasts after treatment with escitalopram was augmented by SHA-68 coadministration. CONCLUSIONS: Early pharmacological effects of escitalopram may be at least partly connected with local NPSR-related alterations of neuroblast maturation in the rat hippocampus. Escitalopram may affect neuropeptide and DCX-expression starting even from the first dose. Adult neurogenesis may be regulated via paracrine neuropeptide S and NMU-related signaling.

Escitalopram alters the hypothalamic OX system but does not affect its up-regulation induced by early-life stress in adult rats.

We hypothesized that there is a relationship between the orexinergic system (OX) alterations and changes elicited by escitalopram or venlafaxine in adult rats subjected to maternal separation (MS). This animal model of childhood adversity induces long-lasting consequences in adult physiology and behavior. Male Wistar rats from the control and MS groups were injected with escitalopram or venlafaxine (10 mg/kg) IP from postnatal day (PND) 69-89. Adult rats were subjected to behavioral assessment, estimation of hypothalamic-pituitary-adrenal (HPA) axis activity and analysis of the OX system (quantitative PCR and immunohistochemistry) in the hypothalamus and amygdala. MS caused anxiety- and depressive-like behavior, endocrine stress-related response, and up-regulation of the OX system in the hypothalamus. Escitalopram, but not venlafaxine, increased the activity of hypothalamic OX system in the control rats and both drugs had no effect on OXs in the MS group. The disturbed signaling of the OX pathway may be significant for harmful long-term consequences of early-life stress. Our data show that the normal brain and brain altered by MS respond differently to escitalopram. Presumably, anti-anxiety and antidepressant effects of this drug do not depend on the activity of hypothalamic OX system.

Predictive efficiency of phoenixin, spexin and kisspeptin neuropeptides concentration levels in diagnosis of bipolar disorder in paediatric population. / Skutecznosc predykcyjna stezen neuropeptydów: feniksyny, speksyny i kisspeptyny dla diagnozy choroby afektywnej dwubiegunowej w populacji pediatrycznej.

OBJECTIVES: The aim of the study was to assess concentrations of the following neuropeptides: phoenixin, spexin and kisspeptin in venous blood serum of children and adolescents suffering from bipolar disorder, and by this their predictive efficiency in this disorder. METHODS: The study covered 75 individuals with a mean age of 15.26 years (95% CI: 14.86-15.67), of which the study group comprised of 57 individuals diagnosed with bipolar affective disorder and the control group - 18 individuals with no psychiatric diagnosis and no pharmacological treatment. Phoenixin, spexin and kisspeptin levels were determined in the peripheral venous blood serum. Neuropeptide concentrations were measured with the enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean phoenixin concentration in the studied group equalled 1.57 ng/ml (95% CI: 1.35-1.79), while in the control group - 2.69 ng/ml (95% CI: 2.38-3; U Mann-Whitney test p-value < 0.05). For spexin, these results were 639.65 pg/ml (95% CI: 558.86-720.44) in the studied group, and 354.28 pg/ml (95% CI: 310.33-398.22; U Mann-Whitney test p-value < 0.05) in the control group. The observed differences were statistically significant. The mean concentration of kisspeptin levels in the studied group was 126.02 pg/ml (95% CI: 39.82-212.23; median: 59.85), while in the control group - 54.83 pg/ml (95% CI: 39.23-70.43; median: 51.3; U Mann-Whitney test p-value = 0.29), and the observed difference was not statistically significant. CONCLUSIONS: The occurrence of bipolar disorder symptoms is statistically significantly linked with a decreased phoenixin concentration and to a small degree - with an increased spexin concentration in blood serum of patients. However, it is not linked with the kisspeptin concentration.

Antipsychotics increase steroidogenic enzyme gene expression in the rat brainstem.

BACKGROUND: Neurosteroids are involved in several important brain functions and have recently been considered novel players in the mechanic actions of neuropsychiatric drugs. There are no reports of murine studies focusing on the effect of chronic neurosteroid treatment in parallel with antipsychotics on key steroidogenic enzyme expression and we therefore focused on steroidogenic enzyme gene expression in the brainstem of rats chronically treated with olanzapine and haloperidol. METHODS AND RESULTS: Studies were carried out on adult, male Sprague-Dawley rats which were divided into 3 groups: control and experimental animals treated with olanzapine or haloperidol. Total mRNA was isolated from homogenized brainstem samples for RealTime-PCR to estimate gene expression of related aromatase, 3ß-HSD and P450scc. Long-term treatment with the selected antipsychotics was reflected in the modulation of steroidogenic enzyme gene expression in the examined brainstem region; with both olanzapine and haloperidol increasing aromatase, 3ß-HSD and P450scc gene expression. CONCLUSIONS: The present findings shed new light on the pharmacology of antipsychotics and suggest the existence of possible regulatory interplay between neuroleptic action and steroidogenesis at the level of brainstem neuronal centres.

Spider Neurotoxins as Modulators of NMDA Receptor Signaling.

Molecules that selectively act on N-methyl-D-aspartate (NMDA) receptors may have a multidirectional effect by modulating the activity of NMDARs, affecting their active sites as well as by changing the composition of their subunits. The results of the clinical trials conducted so far in mood disorders and schizophrenia indicate that such agents may become new effective drugs for the treatment of these diseases. Number of spider neurotoxins e.g. ctenitoxins extracted from Phoneutria sp. venom act as potent and selective NMDAR blockers that do not disturb cortical and hippocampal glutamate signaling, LTP generation and synaptic neurochemistry. Possibly this intriguing kind of promising neuroregulatory peptides and polyamines can be clinically applicable in a wide spectrum of neuropsychiatric disorders, including epilepsy, neurotrauma and ischemic injuries. These novel medications can potentially be helpful in the future treatment of stroke and several neurodegenerative diseases.

Amantadine in the Treatment of Sexual Inactivity in Schizophrenia Patients Taking Atypical Antipsychotics-The Pilot Case Series Study.

Sexual dysfunctions in people with schizophrenia are more severe than in the general population and are an important element in the treatment of schizophrenia. The mechanism of sexual dysfunction in patients treated for schizophrenia may be related to the side effects of antipsychotic drugs (hyperprolactinemia, suppression of the reward system), but it may also be related to the pathogenesis of schizophrenia itself. The aim of the study was to present the possibility of using amantadine in the treatment of sexual dysfunction in schizophrenia without the concomitant hyperprolactinemia. In an open and naturalistic case series study, five men treated for schizophrenia in a stable mental state were described. All patients reported a prolonged lack of sexual desire and sexual activity prior to treatment with amantadine. After exclusion of hyperprolactinemia, patients received amantadine 100 mg in the evening. Sexual dysfunction was assessed using subscales of the 14-point Short Form of the Changes in Sexual Functioning Questionnaire (CSFQ-14). On subsequent visits after 1, 2 and 3 months of administration of amantadine, an improvement in sexual functioning was observed in all patients. Although this is only the preliminary report, amantadine may become a new indication for the treatment of sexual dysfunction in schizophrenia patients.

Neuropeptides of the human magnocellular hypothalamus.

Hypothalamic magnocellular nuclei with their large secretory neurons are unique and phylogenetically conserved brain structures involved in the continual regulation of important homeostatic and autonomous functions in vertebrate species. Both canonical and newly identified neuropeptides have a broad spectrum of physiological activity at the hypothalamic neuronal circuit level located within the supraoptic (SON) and paraventricular (PVN) nuclei. Magnocellular neurons express a variety of receptors for neuropeptides and neurotransmitters and therefore receive numerous excitatory and inhibitory inputs from important subcortical neural areas such as limbic and brainstem populations. These unique cells are also densely innervated by axons from other hypothalamic nuclei. The vast majority of neurochemical maps pertain to animal models, mainly the rodent hypothalamus, however accumulating preliminary anatomical structural studies have revealed the presence and distribution of several neuropeptides in the human magnocellular nuclei. This review presents a novel and comprehensive evidence based evaluation of neuropeptide expression in the human SON and PVN. Collectively this review aims to cast a new, medically oriented light on hypothalamic neuroanatomy and contribute to a better understanding of the mechanisms responsible for neuropeptide-related physiology and the nature of possible neuroendocrinal interactions between local regulatory pathways.

Possible Antidepressant Effects of Memantine-Systematic Review with a Case Study.

The treatment of bipolar depression is hampered by the inadequate efficacy of antidepressants, moderate effect of mood stabilizers, and the side effects of some second-generation antipsychotics. There is limited evidence to date regarding the antidepressant effects of memantine in bipolar depression. The aim of the article was to provide a short review of preclinical and clinical studies on the antidepressant effect of memantine, and to present the case of a bipolar depression patient successfully treated with memantine. The described patient with bipolar disorder was unsuccessfully treated with two mood stabilizers. The addition of memantine at a dose of 20 mg/d to the treatment with lamotrigine and valproic acid resulted in a reduction in the severity of depression measured on the HDRS-17 scale by 35%, and by 47.1% after 7 weeks. The discussion presents experimental evidence for the antidepressant effect of memantine, as well as data from clinical trials in recurrent and bipolar depression. The presented case is the second report in the medical literature showing the antidepressant effect of memantine as an add-on treatment for bipolar depression. The described case and literature analysis indicate that memantine may be an effective and safe method of augmentation of mood stabilizing therapy in bipolar depression.