Brain Research. Molecular Brain Research

Kinesin participates in axonal transport of neurofilaments (NFs), but the mode by which they attach to kinesin is unclear. We compared the association of NFs with kinesin in mice expressing or lacking NF-H or NF-M. In normal and M-/- mice, the leading edge of metabolically labeled NF subunits was selectively co-precipitated with kinesin. By contrast, the entire wave of radiolabeled subunits co-precipitated with kinesin in H-/- mice. Similar bulk levels of NFs co-precipitated with kinesin from normal and H-/- mice, but reduced levels co-precipitated from M-/- mice...

As a member of family of cytosolic calcium binding proteins, Calbindin-D9k (CaBP-9k) is expressed in female reproductive system and regulated by steroid hormones, estrogen (E2) and progesterone (P4), but its expression and role in pituitary gland have not been elucidated yet. Thus, in this study, we elucidated the expression of CaBP-9k mRNA and protein in pituitary gland of rats. During estrous cycle of rats, pituitary CaBP-9k level fluctuated, and its mRNA was highly elevated during an E2-dominant stage (proestrus and estrus), whereas its level disappeared at a P4-dominant stage (metestrus and diestrus)...

Aquaporin (AQP) 4 is a member of the AQP gene family of water-selective transport proteins. We studied the effect of water deprivation on AQP4 gene expression in chickens. The nucleotide sequence of a chicken aquaporin 4 (AQP4) cDNA that encodes a protein of 335 amino acids showed high homology to mammalian AQP4. Using Northern blotting analysis, AQP4 mRNA in chickens was observed as a band of approximately 5.5 kb in several tissues in addition to the hypothalamus, proventriculus, kidney, and breast muscle...

Barhl1 and Brn-3c have been identified as transcription factors that are essential for survival and maintenance of hair cells of the inner ear. Little is known about the mechanism of how Brn-3c or Barhl1 may regulate transcription in the inner ear. In this study, the transcriptional function of both Brn-3c and Barhl1 was investigated in the organ-of-Corti-derived cell lines, OC-1 and OC-2. We examined regulatory domains in these transcription factors by linking regions of Barhl1 and Brn-3c to the DNA binding domain of the heterologous transcription factor GAL4 and assayed their effect on a heterologous promoter containing GAL4 DNA binding sites by co-transfection into OC-1 and OC-2 cell lines...

Parkinson's disease is characterized by a severe loss of dopaminergic neurons resulting in a range of motor deficits. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain with corresponding Parkinsonian symptoms. Several animal species have also shown sensitivity to MPTP, including primates, mice, goldfish, and, most recently, zebrafish. This study demonstrates that the effect of MPTP on dopaminergic neurons in zebrafish larvae is mediated by the same pathways that have been demonstrated in mammalian species...

GABA and glutamate are the major neurotransmitters in the human central nervous system. Disturbances in these transmitter systems have been suggested to influence a variety of neurological and psychiatric diseases. Human platelets have been used as a model for neural amino acid transport, although it has not been known exactly which transporters participate in the transport process. In this study, we identify with reverse transcription-polymerase chain reaction (RT-PCR) BGT-1 and EAAT3 as transporters for GABA and glutamate, respectively...

Neurons in the hilus of the dentate gyrus are lost following a lateral fluid percussion injury. Environmental enrichment is known to increase neurogenesis in the dentate in intact rats, suggesting that it might also do so following fluid percussion injury, and potentially provide replacements for lost neurons. We report that 1 h of daily environmental enrichment for 3 weeks increased the number of progenitor cells in the dentate following fluid percussion injury, but only on the ipsilesional side. In the dentate granule cell layer, but not the hilus, most progenitors had a neuronal phenotype...

It has been reported that several of the effects induced by an octadecaneuropeptide (ODN), derived from an 86-amino-acid polypeptide termed diazepam-binding inhibitor, could be mediated by activation of a metabotropic receptor. In order to investigate the role and mechanism of action of ODN in the regulation of corticotropin-releasing factor (CRH) and neuropeptide Y (NPY) expression in the paraventricular nucleus and arcuate nucleus, respectively, we studied the effects of the acute intracerebroventricular administration of ODN (2 microg/rat) and the ODN antagonist to metabotropic receptor, cyclo(1-8)[Dleu5]OP (20 microg/rat), on the gene expression of the two neuropeptides in castrated male rat...

GABA, the major inhibitory neurotransmitter of the vertebrate brain, has been shown to play an important role in vertebrate reproduction by regulating LH release and sexual behavior. We have studied the expression of the GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), in goldfish throughout the reproductive cycle in May (mature), November (early gonadal recrudescence) and February (late gonadal recrudescence) and in response to implanted sex steroids. Levels of GAD67 and GAD65 mRNA levels in the hypothalamus of both males and females were highest in the early stages of gonadal recrudescence...

We have tested the effect of deprenyl on the neurotoxicity induced by the injection of quinolinic acid within the striatum. Deprenyl was unable to prevent these quinolinic acid-induced damages, but enhanced the loss of several gamma-aminobutyric acid (GABA) positive subpopulations, the loss of the astroglial population and the activation of microglia produced by quinolinic acid. These effects are produced by deprenyl potentiation of dopamine actions since dopamine depletion produced by previous injection of the dopaminergic toxin 6-hydroxydopamine within the medial forebrain bundle overcomes deprenyl effects and the involvement of dopamine in the quinolinic acid-induced toxicity in striatum...

The response to stress is influenced by prior experience with the same or different stressor. For example, exposure of cold pre-stressed rats to heterotypic (novel) stressors, such as immobilization (IMO), triggers an exaggerated release of catecholamines and increase in gene expression for adrenomedullary tyrosine hydroxylase (TH), the rate limiting catecholamine biosynthetic enzyme. To study the mechanism, we examined induction or phosphorylation of several transcription factors, which are implicated in IMO-triggered regulation of TH transcription, in rats exposed to cold (4 degrees C) for up to 28 days and then subjected to IMO...

Delphilin is identified as a Glutamate receptor delta2 (GluRdelta2) subunit interacting protein, consisting of a PDZ domain and formin homology (FH) domains 1 and 2, in addition to a C-terminal coiled-coil structure. Delphilin has been shown to be selectively expressed in cerebellar Purkinje cells where it co-localizes with the GluRdelta2 subunit at the Purkinje cell-parallel fiber synapses. Although Delphilin specifically interacts with the GluRdelta2 C-terminus via its PDZ domain, the physiological role of the interaction is not yet understood...

Neuronal injury in manganism is accompanied by activation of astroglia within the basal ganglia that is thought to increase production of inflammatory mediators such as nitric oxide (NO). The present studies postulated that astroglial-derived NO mediates neuronal apoptosis induced by manganese (Mn) and pro-inflammatory cytokines. Pheochromocytoma (PC12) cells differentiated with nerve growth factor (NGF) were co-cultured with primary astrocytes and exposed to Mn and tumor necrosis factor-alpha (TNF-alpha) plus interferon-gamma (IFN-gamma)...

Kainic acid activates non-N-methyl-d-aspartate (NMDA) glutamate receptors where it increases synaptic activity resulting in seizures, neurodegeneration, and remodeling. We performed microarray analysis on rat hippocampal tissue following kainic acid treatment in order to study the signaling mechanisms underlying these diverse processes in an attempt to increase our current understanding of mechanisms contributing to such fundamental processes as neuronal protection and neuronal plasticity. The kainic acid-treated rats used in our array experiments demonstrated severe seizure behavior that was also accompanied by neuronal degeneration which is suggested by fluoro-jade B staining and anti-caspase-3 immunohistochemistry...

Potassium channels containing the KCNQ2 subunit play an important role in the regulation of neuronal excitability and therefore have been implicated in epilepsy. This study describes the expression of KCNQ2 subunit immunoreactivity in the basolateral amygdala in two rat models of temporal lobe epilepsy, (1) amygdala kindling and (2) spontaneously epileptic rats after status epilepticus induced by hippocampal electrical stimulation. KCNQ2 subunit immunoreactivity was assessed with a commercial antibody raised against a C-terminal part of the KCNQ2 protein...

Most CNS studies using recombinant adeno-associated virus type 2 (rAAV-2) vectors have focused on gene delivery for the purpose of gene therapy. In the present study, we examined the feasibility of using rAAV-2 vectors to study the regulation of preprotachykinin-A (PPT-A) promoter activity in striatal medium spiny projection neurons. An rAAV-2 vector incorporating a PPT promoter fragment (shown previously to confer some cell-specificity of expression in vitro) coupled to a green fluorescent protein (GFP) reporter gene was stereotaxically injected into the rat striatum...

Recent studies have identified a new family of gap junction-forming proteins in vertebrates, called pannexins. Although their function in vivo is still not known, studies in Xenopus oocytes have indicated that pannexin1 (Px1) and pannexin2 (Px2) can form functional gap junction channels and can contribute to functional hemichannels. In this study, we have utilized a combination of radioactive and non-radioactive in situ hybridization experiments to characterize the expression pattern of the two pannexin genes during development and maturation of the rat brain...

SPARC is a matricellular protein that modulates cell-cell and cell-matrix interactions by virtue of its antiproliferative and counteradhesive properties. Here, we report the denervation-induced upregulation of SPARC mRNA and protein in the mouse hippocampus following transections of the entorhinal afferents. Northern blot analysis showed that SPARC mRNA was upregulated in a transient manner in the deafferented mouse hippocampus. In situ hybridization and immunohistochemistry confirmed the temporal upregulation of both SPARC mRNA and protein specifically in the denervated areas, which initiated at 7 days postlesion, reached the maximum at 15 as well as 30 days postlesion, and subsided towards normal levels by 60 days postlesion...

Brn-3a is a transcription factor expressed in a subset of neurons of the peripheral nervous system. Its role encompasses the activation of genes involved in neuronal differentiation and survival. While a lot of data have been produced on Brn-3a target promoters, very little is known about the upstream regulatory signals that mediate its activation in response to differentiation. In this work, we describe for the first time that Brn-3a is phosphorylated in IMR-32 neuroblastoma cells in response to differentiation induced by retinoic acid treatment and that its post-translational modification is potentially mediated by the activation of the MAPK/ERK pathway...

Neuropathy target esterase (NTE) is inhibited and aged by organophosphorus compounds that induce delayed neuropathy in human and some sensitive animals. NTE has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation. However, to date, there is no direct evidence of the relevance of NTE in neurodifferentiation under physiological conditions. In this study, we have investigated a possible role for NTE in the all-trans retinoic acid-induced differentiation of neuroblastoma cells...