Alterations in pituitary adenylate cyclase-activating polypeptide in major depressive disorder, bipolar disorder, and comorbid depression in Alzheimer's disease in the human hypothalamus and prefrontal cortex.

Background: Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is involved in the stress response and may play a key role in mood disorders, but no information is available on PACAP for the human brain in relation to mood disorders.

Methods: PACAP-peptide levels were determined in a major stress-response site, the hypothalamic paraventricular nucleus (PVN), of people with major depressive disorder (MDD), bipolar disorder (BD) and of a unique cohort of Alzheimer's disease (AD) patients with and without depression, all with matched controls. The expression of PACAP-(Adcyap1mRNA) and PACAP-receptors was determined in the MDD and BD patients by qPCR in presumed target sites of PACAP in stress-related disorders, the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC).

A quantitative in situ hybridization protocol for formalin-fixed paraffin-embedded archival post-mortem human brain tissue.

The use of radioactive in situ hybridization (ISH) to quantitatively determine low-to-moderate abundant mRNA expression in formalin-fixed, paraffin-embedded archival post-mortem human brain tissue is often limited by non-specific-deposits, visible as speckles. In the present study, optimal hybridization conditions were achieved for quantifying the mRNA expression of histidine decarboxylase (HDC) by a number of alterations in a routine protocol, which included (1) during purification of the oligo-probes, glycogen was omitted as a carrier for precipitation, (2) after precipitation, the labeled probe contained within the pellet was first dissolved in water instead of in hybridization buffer (HBF), (3) during hybridization, the dithiothreitol (DTT) concentration was increased from 200 to 800 mM in HBF, and (4) stringencies during hybridization and post-hybridization washes were increased by increasing the temperature. The effect of the adjustment was quantified on adjacent sections from 18 subjects (9 with Parkinson's disease and 9 controls), by comparing the data from the standard and new protocol.

Differential effects of lentiviral vector-mediated overexpression of nerve growth factor and glial cell line-derived neurotrophic factor on regenerating sensory and motor axons in the transected peripheral nerve.

Even after reconstructive surgery, major functional impairments remain in the majority of patients with peripheral nerve injuries. The application of novel emerging therapeutic strategies, such as lentiviral (LV) vectors, may help to stimulate peripheral nerve regeneration at a molecular level. In the experiments described here, we examined the effect of LV vector-mediated overexpression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on regeneration of the rat peripheral nerve in a transection/repair model in vivo.

Neuroregenerative effects of lentiviral vector-mediated GDNF expression in reimplanted ventral roots.

Traumatic avulsion of spinal nerve roots causes complete paralysis of the affected limb. Reimplantation of avulsed roots results in only limited functional recovery in humans, specifically of distal targets. Therefore, root avulsion causes serious and permanent disability.

Increased metabolic activity in nucleus basalis of Meynert neurons in elderly individuals with mild cognitive impairment as indicated by the size of the Golgi apparatus.

In this study, we examined the metabolic activity of nucleus basalis of Meynert (NBM) neurons in individuals clinically diagnosed with no cognitive impairment (NCI, n = 8), mild cognitive impairment (MCI, n = 9), and subjects with moderate Alzheimer disease (AD, n = 7). We used Golgi apparatus (GA) size as a measure of neuronal metabolic activity. Subjects with MCI showed increased NBM metabolic activity; they had significantly more neurons with larger GA size as compared with NCI and AD subjects.

Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report.

Background: Elevated arginine vasopressin (AVP) plasma levels have been observed in major depression, particularly in relation to the melancholic subtype. Two hypothalamic structures produce plasma vasopressin: the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). The aim of this study was to establish which structure is responsible for the increased vasopressin plasma levels in depression.

Absence of a difference in the neurosecretory activity of supraoptic nucleus vasopressin neurons of neuroleptic-treated schizophrenic patients.

Dysfunction in water intake and metabolism has frequently been reported in schizophrenia. The general population of schizophrenics under neuroleptic treatment secretes lower amounts of vasopressin than controls at comparable values of plasma osmolality. The purpose of the present study was to investigate the synthetic activity of vasopressin neurons of the dorsolateral supraoptic nucleus in schizophrenia on postmortem material using a battery of histochemical activity markers.

Multi-transcriptional profiling of melanin-concentrating hormone and orexin-containing neurons.

1.Melanin-concentrating hormone (MCH) and orexin-containing neurons participate in hypothalamic circuits that control energy homeostasis. While these two systems have projections to widespread target areas within the central nervous system, little is known about intrinsic characteristics and the molecular composition of both the MCH and orexin neurons themselves.

Increased melanin concentrating hormone receptor type I in the human hypothalamic infundibular nucleus in cachexia.

Melanin-concentrating hormone (MCH) exerts a positive regulation on appetite and binds to the G protein-coupled receptors, MCH1R and MCH2R. In rodents, MCH is produced by neurons in the lateral hypothalamus with projections to various hypothalamic and other brain sites. In the present study, MCH1R was shown, by immunocytochemistry, to be present in the human infundibular nucleus/median eminence, paraventricular nucleus, lateral hypothalamic area, and perifornical area, although in the latter two regions, only a few MCH1R-containing cells were found.

Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury.

Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF).

Estrogen receptors and metabolic activity in the human tuberomamillary nucleus: changes in relation to sex, aging and Alzheimer's disease.

The human tuberomamillary nucleus (TMN), that is the sole source of histamine in the brain, is involved in arousal, learning and memory and is impaired in Alzheimer's disease (AD) as shown by the presence of cytoskeletal alterations, a reduction in the number of large neurons, a diminished neuronal metabolic activity and decreased histamine levels in the hypothalamus and cortex. Experimental data and the presence of sex hormone receptors suggest an important role of sex steroids in the regulation of the function of TMN neurons. Therefore, we investigated sex-, age- and Alzheimer-related changes in estrogen receptor alpha and beta (ERalpha and ERbeta) in the TMN.

Human basal cortisol levels are increased in hospital compared to home setting.

The impact of study-environment on experimental outcome is mostly not realized and certainly not demonstrated. In the present study, a comparison was made between free salivary cortisol levels in healthy young men in a carefully controlled hospital setting versus a home setting. Cortisol levels during rest were increased in hospital compared to home environment: 2-fold at awakening, 3-fold at the morning peak, and 5-fold late in the evening.

Oxytocin Neurotransmission in the A1-area of the Brainstem Induces Hormonal Vasopressin Release in Rats.

To investigate the role of the oxytocin innervation of the caudal ventrolateral medulla, immunocytochemical techniques were used to demonstrate the presence of oxytocin fibres and terminals in close apposition to noradrenergic neurons of the A1-area. Subsequently, in freely moving animals fitted with an indwelling jugular venous catheter and a bilaterally implanted chronic cannula in the A1-area, it was examined whether infusions of oxytocin in this area were able to influence hormonal vasopressin release. It appeared that nanomolar (50-500 nM) concentrations of oxytocin induce a fourfold rise in plasma vasopressin values.