Neuroscience
-
Comparative Study
Comparison of motor performance, brain biochemistry and histology of two A30P α-synuclein transgenic mouse strains.
Three point mutations in the SNCA gene encoding α-synuclein (aSyn) have been associated with autosomal dominant forms of Parkinson's disease. To better understand the role of the A30P mutant aSyn, we compared two transgenic mouse strains: a knock-in mouse with an introduced A30P point mutation in the wild-type (WT) gene (Snca(tm(A30P))) and a transgenic (Tg) mouse overexpressing the human A30P aSyn gene under the prion promoter [tg(Prnp-SNCA A30P)]. The brain aSyn load, motor performance, brain dopamine (DA) and sensitivity to 6-hydroxydopamine (6-OHDA) were studied in these mice. aSyn was evidently accumulating with age in all mice, particularly in tg(Prnp-SNCA A30P) Tg mice. ⋯ This ratio and homovanillic acid/DA-ratio were declined in Snca(tm(A30P)) mice. Our results demonstrate that the two differently constructed A30P-aSyn mouse strains have distinct behavioral and biochemical characteristics, some of which are opposite. Since the two lines with the same background were not identically produced, the deviations found may be partially caused by factors other than aSyn-related genetic differences.
-
This study was designed to examine the effects of chronic running exercise (Ex) on the hypobaric hypoxia-induced neuronal injury in the hippocampus. Male Wistar rats (9 weeks old) were caged in a hypoxic altitude chamber simulating the condition of 9,000 m high (0.303 atm) for 7h and the brains were examined at 0, 4, and 24h after treatment. Hypoxia challenge increased the levels of caspase 3 (mean ± SEM, % of baseline control, 121.9 ± 11.8, 152.3 ± 15.3, 141.6 ± 7.0 for 0, 4 and 24h, respectively, n=5) and induced apoptosis (cell number, 205.7 ± 8.8, 342.3 ± 33.4, 403.0 ± 12.2 for 0, 4 and 24h vs. 7.7 ± 1.4 baseline control, n=3) in the hippocampal CA1 pyramidal neurons. ⋯ Taken together, our results show that chronic Ex protects hippocampal CA1 neurons against hypobaric hypoxia insult. Ex-enhanced bioenergetic adaptation and anti-oxidative capacity may prevent neurons from hypoxia-induced apoptosis. Furthermore, activation of the BDNF signaling pathway may be involved in the Ex-induced protection.
-
The relationship between learning/memory performance and long-term potentiation (LTP) induction is ambiguous. Although a large body of data supports a strong correspondence between learning/memory performance and LTP, many studies have also provided evidence to the contrary. In this study, we found that 2-month-old senescence-accelerated mice/prone 8 (SAMP8 mice) displayed both impaired performance in a Morris Water Maze (MWM) and enhanced LTP compared to senescence-accelerated mice/resistance 1 (SAMR1). ⋯ Further analysis demonstrated that the increase in cytokine content was higher in the hippocampal tissues used for LTP recording in the SAMR1 and CFA-challenged animals compared to the SAMP8 and intact BALB/c mice. A correlation analysis demonstrated that pro-inflammatory cytokines (IL-6 and TNF-α) displayed a negative correlation with LTP, while an anti-inflammatory cytokine (IL-10) displayed a positive correlation with LTP. These results suggest that pro-inflammatory cytokines induced by LTP manipulation in experiments (e.g., via tissue injury caused by electrode insertion) may be one of the factors contributing to the observed lack of correspondence between memory/learning ability and LTP.
-
Fibronectin type III domain-containing 5 protein (Fndc5) or peroxisomal protein, is a type I membrane protein that has 209 amino acid residues. Previous studies by our group have shown an increase in its expression after retinoic acid treatment of mouse embryonic stem cells (mESCs) during the process of neural differentiation, leading us to conclude that it might be involved in neurogenesis. In the present study, we have constructed an inducible short hairpin RNA (shRNA) vector that is expressed under induction by doxycycline. ⋯ Fndc5 knockdown during both stages significantly affected both neuronal and astrocytes maturation. We have concluded that Fndc5 expression is required for the appropriate neural differentiation of mESCs. These data confirm the importance of Fndc5 in the generation and development of the nervous system.
-
Vascular dementia (VD), defined as a loss of memory and cognitive function resulting from vascular lesions in the brain, is the second-most-common cause of dementia in the elderly, after Alzheimer's disease. In recent years, research has focused on the pathogenesis of VD, and mitochondrial bioenergetic deficits have been suggested to contribute to VD onset. To further investigate the role of mitochondria in VD, we used a rat model of VD, which involved permanent bilateral occlusion of the common carotid arteries (with a 1-week interval between artery occlusion to avoid an abrupt reduction in cerebral blood flow) leading to chronic cerebral hypoperfusion. ⋯ The ischemia group mitochondria also exhibited decreased respiration coupled to decreased expression and activity of the electron transport chain complex IV (cytochrome c oxidase). These results indicate that the mitochondrial oxidative metabolism is inhibited in the hippocampi of rats following chronic ischemia-induced VD. As the mitochondrial oxidative metabolism deficits, namely mitochondrial bioenergetic deficits directly affect the functions of neurons, it may contribute to VD onset.