Chronic stress is the leading cause of memory impairment today. Various stress-based models are being developed for studying cognitive impairment. Repurposing of existing drugs in a new pharmacology class is the safest and cheapest option for treatment instead of new drug discovery. Vorinostat (VOR) is the first histone deacetylase (HDAC) inhibitor approved for the treatment of cutaneous T-cell lymphoma by the U.S. FDA. VOR follows the rule of five and is reported to cross the blood−brain barrier. Therefore, we aimed to evaluate the procognitive potential of VOR (25 mg/kg) administered by intraperitoneal (ip) route in a stress-based model of chronic corticosterone (CORT) injections (20 mg/kg, subcutaneously (sc)). The study comprised six groups. Normal mice were administered vehicle (VEH) (days 1−21, sc) in the first group, VOR (days 8−21, 25 mg/kg, ip) in the second group, and fluoxetine (FLX) (days 8−21, 15 mg/kg, oral) in the third group. Mice in the remaining three groups were given 20 mg/kg (sc) CORT for 21 days, and VOR (days 8−21, 25 mg/kg, ip) or FLX (days 8−21, 15 mg/kg, oral) was additionally administered to the treatment groups. Behavioral tests such as Morris water maze test, novel object recognition test, and object in place test were performed at the end of the dosing schedule to assess cognition. After behavior tests, mice were sacrificed, and hippocampus was separated from brain tissue for reverse transcriptase polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry studies. VOR treatment attenuated endoplasmic reticulum (ER) stress in CORT mice as evident from the reduction in DNA damage-inducible transcript 3 (Ddit3) (gene encoding CHOP), caspase 12 (Casp12), and calpain-2 (Capn2) mRNA levels, and cleaved caspase 3 (CASP3) protein expression. Bax inhibitor-1 (BI-1) was significantly increased in VOR-treated CORT mice. VOR also reversed CORT induced increase in HDAC2 level in the CA3 region. The protective effects of VOR were comparable to that of FLX in CORT mice. Thus, VOR has the potential to reverse cognitive dysfunction via modulation of ER stress markers and HDAC2.
Black Carbon (BC) is a major pollutant that poses immediate health as well as long-term climatic threat to human civilization. Globally, India and China are considered to be among the significant contributors of carbonaceous aerosol. Therefore, in the recent past, several studies on BC measurements have been conducted and reported in both these countries. Optical absorbance measurement techniques which give BC mass by measuring light absorbance of aerosol have been used widely. Keeping these facts in mind, here an attempt has been made to realise the current state of Equivalent Black Carbon (EBC) measurement done in both countries. Eighty EBC measurement studies published in last 15 years (2005–2020) are analysed on the basis of technique, instrumentation and various important parameters involved in measurements. It is found that EBC measurements in India and China contain large uncertainties, and available data are metrologically insufficient to realise spatial distribution and long-term temporal variation precisely. Furthermore, MERRA-2 Surface Black Carbon (SBC) levels and EBC measurements are compared and evaluated for biases between spatial and temporal variation of modelled data and ground measurements. It is observed that standardization of measurement technique and parameters involved in measurement is the need of the hour. Lack of a reference method creates inconsistency and discrepancy among the measurements. Recommendations for selection of parameter/instrument and cautious measures are provided as conclusion based on this review to improve overall metrology of BC.
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