No preliminary evidence of differences in astrocyte density within the white matter of the dorsolateral prefrontal cortex in autism

Background: While evidence for white matter and astrocytic abnormalities exist in autism, a detailed investigation of astrocytes has not been conducted. Such an investigation is further warranted by an increasing role for neuroinflammation in autism pathogenesis, with astrocytes being key players in this process. We present the first study of astrocyte density and morphology within the white matter of the dorsolateral prefrontal cortex (DLPFC) in individuals with autism. Methods: DLPFC formalin-fixed sections containing white matter from individuals with autism (n = 8, age = 4-51 years) and age-matched controls (n = 7, age = 4-46 years) were immunostained for glial fibrillary acidic protein (GFAP). Density of astrocytes and other glia were estimated via the optical fractionator, astrocyte somal size estimated via the nucleator, and astrocyte process length via the spaceballs probe. Results: We found no evidence for alteration in astrocyte density within DLPFC white matter of individuals with autism versus controls, together with no differences in astrocyte somal size and process length. Conclusion: Our results suggest that astrocyte abnormalities within the white matter in the DLPFC in autism may be less pronounced than previously thought. However, astrocytic dysregulation may still exist in autism, even in the absence of gross morphological changes. Our lack of evidence for astrocyte abnormalities could have been confounded to an extent by having a small sample size and wide age range, with pathological features potentially restricted to early stages of autism. Nonetheless, future investigations would benefit from assessing functional markers of astrocytes in light of the underlying pathophysiology of autism

Potential novel biomarkers for diabetic testicular damage in streptozotocin-induced diabetic rats: Nerve growth factor beta and vascular endothelial growth factor

PubMed ID: 24771956Background. It is well known that diabetes mellitus may cause testicular damage. Vascular endothelial growth factor (VEGF) and nerve growth factor beta (NGF-ß) are important neurotrophic factors for male reproductive system. Objective. We aimed to investigate the correlation between testicular damage and testicular VEGF and NGF-ß levels in diabetic rats. Methods. Diabetes was induced by streptozotocin (STZ, 45mg/kg/i.p.) in adult rats. Fiveweeks later testicular tissuewas removed; testicular VEGF and NGF-ß levels were measured by ELISA. Testicular damage was detected by using hematoxylin and eosin staining and periodic acid- Schiff staining, and apoptosis was identified by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). Seminiferous tubular sperm formation was evaluated using Johnsens score. Results. In diabetic rats, seminiferous tubule diameter was found to be decreased; basement membrane was found to be thickened in seminiferous tubules and degenerated germ cells. Additionally, TUNEL-positive cells were increased in number of VEGF+ cells and levels of VEGF and NGF-ß were decreased in diabetic testes. Correlation between VEGF and NGF-ß levels was strong. Conclusion. These results suggest that the decrease of VEGF and NGF-ß levels is associated with the increase of the apoptosis and testicular damage in diabetic rats. Testis VEGF and NGF-ß levels could be potential novel biomarkers for diabetes induced testicular damage. © Copyright 2014 Magorzata Guz et al

Effects of carbon dioxide exposure on early brain development in rats

WOS: 000337900500007PubMed ID: 24476563The developing brain is vulnerable to environmental factors. We investigated the effects of air that contained 0.05, 0.1 and 0.3% CO2 on the hippocampus, prefrontal cortex (PFC) and amygdala. We focused on the circuitry involved in the neurobiology of anxiety, spatial learning, memory, and on insulin-like growth factor-1 (IGF-1), which is known to play a role in early brain development in rats. Spatial learning and memory were impaired by exposure to 0.3% CO2 air, while exposure to 0.1 and 0.3% CO2 air elevated blood corticosterone levels, intensified anxiety behavior, increased superoxide dismutase (SOD) enzyme activity and MDA levels in hippocampus and PFC; glutathione peroxidase (GPx) enzyme activity decreased in the PFC with no associated change in the hippocampus. IGF-1 levels were decreased in the blood, PFC and hippocampus by exposure to both 0.1 and 0.3% CO2. In addition, apoptosis was increased, while cell numbers were decreased in the CA1 regions of hippocampus and PFC after 0.3% CO2 air exposure in adolescent rats. A positive correlation was found between the blood IGF-1 level and apoptosis in the PFC. We found that chronic exposure to 0.3% CO2 air decreased IGF-1 levels in the serum, hippocampus and PFC, and increased oxidative stress. These findings were associated with increased anxiety behavior, and impaired memory and learning

CARNOSINE ATTENUATES OXIDATIVE STRESS AND APOPTOSIS IN TRANSIENT CEREBRAL ISCHEMIA IN RATS

Cerebral ischemia leads to cognitive decline and neuronal damage in the hippocampus. Reactive oxygen species (ROS) play an important role in the neuronal loss after cerebral ischemia and reperfusion injury. Carnosine has both antioxidant and neuroprotective effects against ROS. In the present study, the effects of carnosine on oxidative stress, apoptotic neuronal cell death and spatial memory following transient cerebral ischemia in rats were investigated. Transient ischemia was induced by occlusion of right common carotid artery of rats for 30 min and reperfusion for 24 h or 1 week. Rats received intraperitoneal injection of 250 mg/kg carnosine or saline 30 min prior to experiment. Determination of antioxidant enzyme activities was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining was performed using an In Situ Cell Death Detection Kit. Carnosine treatment elicited a significant decrease in lipid peroxidation and increase in antioxidant enzyme activities in ischemic rat brains. The number of TUNEL-positive cells was decreased significantly in carnosine-treated group when compared with the ischemia-induction group. Carnosine treatment did not provide significant protection from ischemia induced deficits in spatial learning. The results show that carnosine is effective as a prophylactic treatment for brain tissue when it is administered before ischemia without affecting spatial memory

Antioxidant and antiapoptotic activities of deprenyl and estradiol co-administration in aged rat kidney

Aging is a progressive degeneration process in living organisms. Deprenyl is an irreversible monoamine-oxidase B inhibitor which has antioxidant, antiapoptotic and neuroprotective effects. Estradiol is also a neuroprotective and antioxidant hormone. The objective of this study was to determine whether the antioxidative effects of deprenyl can suppress apoptotic activity, with or without estradiol, in aged female rat kidney. Wistar Albino female rats were divided into six groups as follows; young (3 months old) control, aged (24 months old) control, aged deprenyl treated, aged estradiol treated, aged deprenyl plus estradiol treated and sham. All rats except for the sham group were injected for 21 days. Determination of oxidative stress parameter was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining and caspase-3 immunohistochemistry were performed. Deprenyl and estradiol administration, alone or in combination, decreased significantly the levels of lipid peroxidation relative to aged control and sham-injected rats. The number of TUNEL positive cells decreased significantly in deprenyl and estradiol-treated rats compared with aged control and sham rats. Deprenyl and estradiol replacement attenuated age-related changes in renal morphology. The results indicate that deprenyl treatment alone, or in combination with estradiol, may modulate age-related apoptotic changes in rat kidney by decreasing oxidative stress

Effects of exercise and poor indoor air quality on learning, memory and blood IGF-1 in adolescent mice

WOS: 000329846700008PubMed ID: 24050191It is known that regular aerobic exercise enhances cognitive functions and increases blood insulin-like growth factor 1 (IGF-1) levels. People living in urban areas spend most of their time indoors and indoor air quality can affect health. We investigated the effects of aerobic exercise in poor and good air quality environments on hippocampus and prefrontal cortex (PFC) neurons, anxiety, and spatial learning and memory in adolescent mice. Poor air quality impaired spatial learning and memory; exercise did not affect learning or memory impairment. Exercise in a good air quality environment improved spatial learning and memory. Poor air quality increased apoptosis in the hippocampus and PFC. Both exercised and sedentary groups living in a poor air quality environment had lower serum IGF-1 levels than those living in a good air quality environment. Living in a poor air quality environment has negative effects on the hippocampus, PFC and blood IGF-1 levels in adolescent mice, but exercise did not alter the negative effects of poor air quality