Transforming growth factor-β2 increases extracellular matrix proteins in optic nerve head cells via activation of the Smad signaling pathway.

Purpose: Transforming growth factor-β2 (TGF-β2) is associated with glaucomatous neuropathy, primarily via the increased synthesis and secretion of extracellular matrix (ECM) proteins and remodeling of the optic nerve head (ONH). Here, we investigated the signaling pathways used by TGF-β2 to stimulate ECM expression by ONH astrocytes and lamina cribrosa (LC) cells.

Methods: TGF-β2 localization and secretion was examined in human donor tissues and ONH astrocytes and LC cells.

Subtilisin-like proprotein convertase expression, localization, and activity in the human retina and optic nerve head.

Purpose: Subtilisin-like proprotein convertases (SPCs) are a family of calcium-dependent cleavage enzymes that act on dibasic sites of various peptide/protein substrates. The purpose of this study was to investigate the expression, localization, and activity of SPCs in the human retina and optic nerve head.

Methods: mRNA expression of the SPC family in the human retina and optic nerve head tissues was evaluated by quantitative reverse transcription polymerase chain reaction (QRT-PCR).

Cdk5 is involved in NFT-like tauopathy induced by transient cerebral ischemia in female rats.

Although neurofibrillary tangle (NFT) formation is a central event in both familial and sporadic Alzheimer's disease (AD), neither cellular origin nor functional consequence of the NFTs are fully understood. This largely is due to the lack of available in vivo models for neurofibrillary degeneration (NFD). NFTs have only been identified in transgenic mice, bearing a transgene for a rare hereditary neurodegenerative disease, frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP17).

Endovascular middle cerebral artery occlusion in rats as a model for studying vascular dementia.

Vascular dementia (VaD), incorporating cognitive dysfunction with vascular disease, ranks as the second leading cause of dementia in the United States, yet no effective treatment is currently available. The challenge of defining the pathological substrates of VaD is complicated by the heterogeneous nature of cerebrovascular disease and coexistence of other pathologies, including Alzheimer's disease (AD) types of lesion. The use of rodent models of ischemic stroke may help to elucidate the type of lesions that are responsible for cognitive impairment in humans.

Neuroendocrine mechanism for tolerance to cerebral ischemia-reperfusion injury in male rats.

Testosterone has been shown to exacerbate cerebral ischemia-reperfusion injury, which suggests that the well-known stress-induced testosterone reduction could be a protective response. We hypothesized that stress-induced testosterone reduction contributes to ischemia tolerance in cerebral ischemia-reperfusion injury in male rats. In intact male rats, stress was induced by brief anesthesia at 6 h before transient middle cerebral artery occlusion (MCAO).

Mitochondrial localization of estrogen receptor beta.

Estrogen receptors (ERs) are believed to be ligand-activated transcription factors belonging to the nuclear receptor superfamily, which on ligand binding translocate into the nucleus and activate gene transcription. To date, two ERs have been identified: ERalpha and ERbeta. ERalpha plays major role in the estrogen-mediated genomic actions in both reproductive and nonreproductive tissue, whereas the function of ERbeta is still unclear.

Transient cerebral ischemia induces aberrant neuronal cell cycle re-entry and Alzheimer's disease-like tauopathy in female rats.

Aberrant mitosis occurs in many tauopathy-related neurodegenerative diseases and is believed to precede the formation of neurofibrillary tangles. In this study, we report for the first time that transient cerebral ischemia induces aberrant mitotic proteins and hyperphosphorylation of tau protein with neurofibrillary tangle-like conformational epitopes in adult female rat cortex. Following transient cerebral ischemia in rats, initiation of apoptosis precedes and is potentially integrated with subsequent aberrant mitosis and tau hyperphosphorylation.

Role of the GABAA system in behavioral, motoric, and cerebellar protection by estrogen during ethanol withdrawal.

Results of studies from our laboratory have shown that administration of 17beta-estradiol (E(2)) reduces cerebellar neuronal damage during ethanol withdrawal (EW). In the current study, we investigated whether the GABAergic system is involved in the protective effects of E(2) against the EW syndrome. To test this hypothesis, we examined the effects of GABAergic drugs, with and without E(2), on EW sign scores, motoric capacity, and caspase activation.

Estrogen protects the inner retina from apoptosis and ischemia-induced loss of Vesl-1L/Homer 1c immunoreactive synaptic connections.

Purpose: Protective effects of estrogen on nerve cells including retinal neurons have been described previously. However, subcellular effects on synaptic connectivity in mild ischemia more closely resembling ischemic conditions found in diabetic or sickle cell retinopathy and stenosis of the carotid artery have not been identified. The present study quantitatively analyzed effects of estrogen administration on synaptic connections of neurons in the ganglion cell layer (GCL) of the retina.

Expression of p75(NTR) in photoreceptor cells of dystrophic rat retinas.

Although a gene mutation in the Royal College of Surgeons (RCS) dystrophic rat results in defective phagocytosis and in accumulation of debris in the subretinal space, the molecular mechanisms leading to photoreceptor cell death remain unclear. In this study, the expression of p75(NTR), the low-affinity neurotrophin receptor incriminated in the apoptosis of developing neurons, was investigated at various stages of retinal degeneration in dystrophic rats using immunohistochemistry, in situ reverse transcription polymerase chain reaction (RT-PCR), Western blot, and relative RT-PCR. In normal adult retinas, p75(NTR) immunolabeling was observed mainly in the outer limiting membrane, with punctate labeling in the inner nuclear and ganglion cell layers.

Estradiol protects against cerebellar damage and motor deficit in ethanol-withdrawn rats.

On the basis of findings obtained from this study, we hypothesize that the female sex steroid 17beta-estradiol (E(2)) protects against cerebellar neuronal damage and behavioral deficit in rats withdrawn from chronic ethanol exposure. Ovariectomized rats implanted with E(2) or an oil pellet received liquid ethanol (7.5% [wt.