Edaravone Dexborneol ameliorates the cognitive deficits of APP/PS1 mice by inhibiting TLR4/MAPK signaling pathway via upregulating TREM2.

Currently, there are no effective therapeutic agents available to treat Alzheimer's disease (AD). However, edaravone dexborneol (EDB), a novel composite agent used to treat acute ischemic stroke, has recently been shown to exert efficacious neuroprotective effects. However, whether EDB can ameliorate cognitive deficits in AD currently remains unclear.

Testosterone deficiency worsens mitochondrial dysfunction in APP/PS1 mice.

Background: Recent studies show testosterone (T) deficiency worsens cognitive impairment in Alzheimer's disease (AD) patients. Mitochondrial dysfunction, as an early event of AD, is becoming critical hallmark of AD pathogenesis. However, currently, whether T deficiency exacerbates mitochondrial dysfunction of men with AD remains unclear.

Hydralazine inhibits neuroinflammation and oxidative stress in APP/PS1 mice via TLR4/NF-κB and Nrf2 pathways.

Alzheimer's disease (AD) is a common chronic progressive neurodegenerative disorder, and curative treatment has not been developed. The objective of this study was to investigate the potential effects of hydralazine (Hyd, a hypertension treatment drug) on the development process of AD and its mechanisms. We treated 6-month-old male APP/PS1 mice with Hyd for 5 weeks, measured changes in behavior and pathological status, and analyzed differences in gene expression by RNA sequencing.

Nrf2 Deficiency Attenuates Testosterone Efficiency in Ameliorating Mitochondrial Function of the Substantia Nigra in Aged Male Mice.

Reduced testosterone level is a common feature of aging in men. Aging, as a risk factor for several neurodegenerative disorders, shows declined mitochondrial function and downregulated mitochondrial biogenesis and mitochondrial dynamics. Mitochondrial biogenesis and mitochondrial dynamics are crucial in maintaining proper mitochondrial function.

Pentoxifylline Enhances Antioxidative Capability and Promotes Mitochondrial Biogenesis in D-Galactose-Induced Aging Mice by Increasing Nrf2 and PGC-1 through the cAMP-CREB Pathway.

Aging is a complex phenomenon associated with oxidative stress and mitochondrial dysfunction. The objective of this study was to investigate the potential ameliorative effects of the phosphodiesterase inhibitor pentoxifylline (PTX) on the aging process and its underlying mechanisms. We treated D-galactose- (D-gal-) induced aging mice with PTX and measured the changes in behavior, degree of oxidative damage, and mitochondrial ultrastructure and content as well as the expression of nuclear factor erythroid 2-related factor 2- (Nrf2-) mediated antioxidant genes and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha- (PGC-1-) dependent mitochondrial biogenesis genes.

Testosterone ameliorates age-related brain mitochondrial dysfunction.

Brain mitochondrial dysfunction and reduced testosterone levels are common features of aging in men. Although evidence suggests that the two phenomena are interrelated, it is unclear whether testosterone supplementation ameliorates mitochondrial dysfunction in the aging male brain. Here, we show that testosterone supplementation significantly alleviates exploratory behavioral deficits and oxidative damage in the substantia nigra and hippocampus of aging male rats.

Parecoxib alleviates the motor behavioral decline of aged rats by ameliorating mitochondrial dysfunction in the substantia nigra via COX-2/PGE2 pathway inhibition.

Mitochondrial dysfunction manifests as an early event in the substantia nigra (SN) in aging and Parkinson disease. Cyclooxygenase 2 (COX-2), the rate-limiting enzyme in the prostaglandin E2 (PGE2) synthesis pathway, is implicated in aging and age-related neurodegenerative diseases; moreover, inhibition of COX-2 expression has been shown to be neuroprotective for nigrostriatal dopaminergic neurons. However, it is not known whether the neuroprotective effect of COX-2 inhibition is related to improved mitochondrial function during the aging process.

Pentoxifylline enhances antioxidative capability and promotes mitochondrial biogenesis for improving age-related behavioral deficits.

Pentoxifylline (PTX) is a non-specific phosphodiesterase inhibitor with pleiotropic effects that is routinely used to treat peripheral vascular disease. In this study, we tested whether PTX could also counteract the detrimental effects of aging in the brain. To accomplish that, we treated aged rats with PTX and measured resulting behavioral alterations as well as changes in dopaminergic neurochemical levels, oxidative balance markers, mitochondrial function, nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator activated receptor-gamma coactivator 1-alpha (PGC-1α) and downstream gene expression, and cyclic adenosine monophosphate (cAMP) content in the brain.

Testosterone enhances mitochondrial complex V function in the substantia nigra of aged male rats.

Deficits in coordinated motor behavior and mitochondrial complex V activity have been observed in aged males. Testosterone supplementation can improve coordinated motor behavior in aged males. We investigated the effects of testosterone supplementation on mitochondrial complex V function in the substantia nigra (a brain region that regulates motor activity) in aged male rats.

Testosterone propionate activated the Nrf2-ARE pathway in ageing rats and ameliorated the age-related changes in liver.

The present study aimed to evaluate the protective efficacy of testosterone propionate (TP) on age-related liver changes via activation of the nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) pathway in aged rats. Aged rats received subcutaneous injections of TP (2 mg/kg/d, 84 days). Oxidative stress parameters and the expression levels of signal transducer and activator of transcription 5b (STAT5b), Kelch-like ECH associating protein-1 (Keap1), Nrf2, haem oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) in liver tissues were examined to check whether the Nrf2-ARE pathway was involved in the age-related changes in liver.

LncRNAs down-regulate Myh1, Casr, and Mis18a expression in the Substantia Nigra of aged male rats.

In this study, we used high-throughput RNA sequencing to identify mRNAs, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are differentially expressed in the Substantia Nigra (SN) of aged and young rats. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to perform functional annotation of mRNAs that were either differentially expressed themselves (DEMs), targeted by differentially expressed lncRNAs (DELs), or the parents of differentially expressed circRNAs (DECs). A total of 112 DEMs, 163 DELs, and 98 DECs were found in the SN of aged rats.

Amelioratory Effects of Testosterone Propionate on Age-related Renal Fibrosis via Suppression of TGF-β1/Smad Signaling and Activation of Nrf2-ARE Signaling.

Androgen plays a pivotal role in the progression of renal fibrosis. However, whether exogenous androgen treatment to aged male rats can improve the age-related renal fibrosis was not explored. In our study, the changes of morphological structure, renal fibrosis, ultrastructure and renal function, the expressions of extracellular matrix (ECM), matrix metalloproteinases (MMPs) and its tissue inhibitors of metalloproteinases (TIMPs), the expressions of tumor growth factor β1 (TGF-β1)/Smad signaling and oxidative stress parameters as well as nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling were tested in kidney of aged male Wistar rats after subcutaneous testosterone propionate (TP, 2 mg/kg/d, 84-day) injection.

Haloperidol ameliorates androgen-induced behavioral deficits in developing male rats.

The purpose of present study was to infer the potential effects of testosterone increase in some male-based childhood-onset neuropsychiatric disorders, such as Tourette syndrome. Thus, the influence of early postnatal androgen exposure upon the neurobehaviors and its possible neural basis were investigated in the study. Male pup rats received consecutive 14-day testosterone propionate (TP) subcutaneous injection from postnatal day (PND) 7.

Finasteride inhibited brain dopaminergic system and open-field behaviors in adolescent male rats.

Aims: Finasteride inhibits the conversion of testosterone to dihydrotestosterone. Because androgen regulates dopaminergic system in the brain, it could be hypothesized that finasteride may inhibit dopaminergic system. The present study therefore investigates the effects of finasteride in adolescent and early developmental rats on dopaminergic system, including contents of dopamine and its metabolites (dihydroxy phenyl acetic acid and homovanillic acid) and tyrosine hydroxylase expressions both at gene and protein levels.

Testosterone Upregulates the Expression of Mitochondrial ND1 and ND4 and Alleviates the Oxidative Damage to the Nigrostriatal Dopaminergic System in Orchiectomized Rats.

Testosterone deficiency, as a potential risk factor for aging and aging-related neurodegenerative disorders, might induce mitochondrial dysfunction and facilitate the declines of the nigrostriatal dopaminergic system by exacerbating the mitochondrial defects and increasing the oxidative damage. Thus, how testosterone levels influence the mitochondrial function in the substantia nigra was investigated in the study. The present studies showed that testosterone deficiency impaired the mitochondrial function in the substantia nigra and induced the oxidative damage to the substantia nigra as well as the deficits in the nigrostriatal dopaminergic system.

The aberrantly expressed long non-coding RNA in the substantia nigra and corpus striatum of Nrf2-knockout mice.

Nuclear factor erythroid 2 like 2 (Nrf2) functions as a neuroprotective agent in Parkinson's disease (PD). This study aimed to investigate the key long non-coding RNAs (lncRNAs) correlated with Nrf2, which might provide valuable information for the exploration of pathogenesis of PD. The lncRNA and mRNA expression profiling of substantia nigra and corpus striatum of Nrf2 (-/-) mice model was obtained from microarray analysis.

Testosterone Propionate Exacerbates the Deficits of Nigrostriatal Dopaminergic System and Downregulates Nrf2 Expression in Reserpine-Treated Aged Male Rats.

There is a controversy over the effects of testosterone supplements on dopaminergic function. Both neuroprotective and toxic effects of testosterone supplements are reported. The status of oxidative stress seems to explain the neuroprotective or toxic properties of testosterone.

Alleviation of Oxidative Damage and Involvement of Nrf2-ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline.

The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats.

Deficits in coordinated motor behavior and in nigrostriatal dopaminergic system ameliorated and VMAT2 expression up-regulated in aged male rats by administration of testosterone propionate.

The effects of testosterone propionate (TP) supplements on the coordinated motor behavior and nigrostriatal dopaminergic (NSDA) system were analyzed in aged male rats. The present study showed the coordinated motor behavioral deficits, the reduced activity of NSDA system and the decreased expression of vesicular monoamine transporter 2 (VMAT2) in 24 month-old male rats. Long term TP treatment improved the motor coordination dysfunction with aging.

Enhancement of dopaminergic activity and region-specific activation of Nrf2-ARE pathway by intranasal supplements of testosterone propionate in aged male rats.

Unlabelled: The potential influence of intranasal testosterone propionate (InTP) supplements on mesodopaminergic system in aged male rats was investigated by analyzing the exploratory and motor behaviors as well as dopamine neurobiochemical indices. Meanwhile, oxidative stress parameters and pathway of nuclear factor erythroid 2-related factor 2 (Nrf2)-binding antioxidant response elements (Nrf2-ARE) were examined to check whether the Nrf2-ARE pathway was involved in the InTP-induced alteration of mesodopaminergic system in aged male rats. The exploratory and motor behavioral deficits, as well as the reduced expression of dopamine, tyrosine hydroxylase, and dopamine transporter, which indicated the declined activity of mesodopaminergic system, were ameliorated in rats administered with 12-week InTP.

The effects of gonadectomy and binge-like ethanol exposure during adolescence on open field behaviour in adult male rats.

Binge drinking ethanol exposure during adolescence can lead to long-term neurobehavioural damage. It is not known whether the pubertal surge in testosterone that occurs during adolescence might impact the neurobehavioural effects of early ethanol exposure in adult animals. We examined this hypothesis by performing sham or gonadectomy surgeries on Sprague-Dawley rats around postnatal day (P) 23.

Transmembrane-4-L-six-family-1, a potential predictor for poor prognosis, overexpressed in human glioma.

Transmembrane-4-L-six-family-1 (TM4SF1), a tumor-associated antigen, is expressed in various human epithelial malignancies including breast, ovarian, lung, and colon carcinomas. The aim of the present study was to measure TM4SF1 gene expression in human glioma tissues and to investigate its relationship with patient outcome. We measured TM4SF1 expression in tumor tissue from 72 patients with glioma and in eight control brain tissues by means of quantitative reverse transcription-PCR, western blotting, and immunohistochemistry.

Chronic testosterone propionate supplement could activated the Nrf2-ARE pathway in the brain and ameliorated the behaviors of aged rats.

Aging is usually associated with a progressive disruption of the redox balance leading to recurrent damage resulting from oxidative stress. Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of motor behavior disorders. Therefore, antioxidant therapies have received considerable attention in motor behavior defects treatment.

Amelioratory effects of testosterone propionate supplement on behavioral, biochemical and morphological parameters in aged rats.

Testosterone has been shown to affect motor behavior and nigrostriatal dopaminergic (NSDA) system in young and adult male rats. However, it is not known whether exogenous testosterone intervention to aged male rats can ameliorate age-related motor impairment. Thus, in the present study, the open field motor behavior and adhesive tape removal motor performance as well as the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) of NSDA system were examined in aged male rats following chronic subcutaneous injections of testosterone propionate (TP).