ABSTRACT
Abstract ................................................................................................. 359 9.1 Introduction .................................................................................. 359 9.2 Materials and Methods ................................................................. 361
9.2.1 Animals ............................................................................ 361 9.2.2 Chemicals ........................................................................ 362 9.2.3 Induction of T2DM .......................................................... 362 9.2.4 Induction of Repeated CRS Procedure ........................... 362 9.2.5 The Experimental Design ................................................ 362 9.2.6 Estimation of Plasma Glucose and Triglyceride (TG)
Level ................................................................................. 363 9.2.7 Estimation of Plasma CORT Level .................................. 364 9.2.8 Estimation of Ulcer Index ................................................ 364 9.2.9 Assessment of Mitochondrial Function, Integrity,
and Oxidative Stress ......................................................... 364 9.2.10 Data Analysis ................................................................ 367
9.3 Discussion .................................................................................... 367 9.4 Results .......................................................................................... 374
9.4.1 The Alteration in Biochemical Parameters such as
Plasma Glucose, TG, and CORT Level in Temporally Treated Repeated Stress on Type-2 Diabetic Rats ............ 374
9.4.2 The Effect of Repeated CRS on Diabetic Rats Relative to STZ-Induction on Ulcer Index ....................... 377
9.4.3 Temporal Effect of Repeated CRS Challenged Diabetic Rats on Mitochondrial Function and Integrity in Different Brain Regions ............................................... 378
9.4.4 Mitochondrial Oxidative Stress in Different Brain Regions is Modulated by the Repeated CRS Treatment to Diabetic Rats at Different Time Point of Diabetes Induction ........................................................................... 379
9.4.5 Serotonergic System in Different Brain Regions of Diabetic Rats is Altered by the Temporal Effect of Repeated CRS .................................................................. 382
9.4.6 Modulation of Noradrenergic (NE) System in Different Brain Regions of Diabetic Rats by the Temporal Effect of Repeated CRS ................................... 384
9.4.7 Temporal Effect of Repeated CRS on Dopaminergic System in Different Brain Regions of Diabetic rats ......... 385
Keywords .............................................................................................. 388 Acknowledgment .................................................................................. 388 References ............................................................................................. 389
ABSTRACT
Type-2 diabetes mellitus patients are susceptible to stressors. The study evaluates the temporal effect of repeated stress in the pathophysiology of T2DM. The T2DM was induced in rats by streptozotocine (STZ, 45 mg/kg, i.p.) and nicotinamide (110 mg/kg, i.p.). Two exposures of cold restraint stress (CRS) were given 24 hr apart, before STZ injection (prediabetes) and after STZ injection (post-diabetes) to separate groups. The stress control group was exposed to two exposures of CRS. Repeated stress potentiates the pathobiogenesis of T2DM and T2DM aggravates the effect of repeated stress. Further, repeated stress after diabetes induction aggravates diabetes-induced metabolic parameters compared to before diabetes induction. Monoaminergic system, mitochondrial function, and integrity were evaluated in discrete brain regions such as, hippocampus (HIP), hypothalamus (HYP), prefrontal cortex (PFC), striatum (STR), amygdala (AMY), and nucleus accumbens (NAC). Diabetes, repeated stress and stress exposed diabetic rats showed region-specific changes in brain monoaminergic system, mitochondrial dysfunction and loss of integrity. Consequently, brain region-specific changes in oxidative damage and attenuated antioxidant defense system were observed. Temporal differences in brain monoaminergic system, mitochondrial dysfunction, integrity, oxidative damage, and reduced antioxidant defenses were found in both pre and post-diabetes stress exposed rodents. Thus, even though repeated stress exacerbates the physiological consequences of T2DM, it reported differences in the pattern of monoaminergic system, mitochondrial dysfunction in different brain regions. Hence, there are differences in the pathophysiology of stress, diabetes, and stress exposed diabetic conditions. Thus, different treatment paradigms may have to be developed other than conventional therapies to treat these conditions.
