Glucocorticoid receptor blockade normalizes hippocampal alterations and cognitive impairment in streptozotocin-induced type 1 diabetes mice.

Type 1 diabetes is a common metabolic disorder accompanied by an increased secretion of glucocorticoids and cognitive deficits. Chronic excess of glucocorticoids per se can evoke similar neuropathological signals linked to its major target in the brain, the hippocampus. This deleterious action exerted by excess adrenal stress hormone is mediated by glucocorticoid receptors (GRs).

Steroid protection in aging and age-associated diseases.

Neuroactive steroids are secretory products of peripheral endocrine glands that modulate a variety of brain functions. A close relationship between neuroactive steroid structure and function becomes most evident under pathological circumstances. On one side, overproduction of glucocorticoid and mineralocorticoid neuroactive steroids may be detrimental to the hippocampus, which is enriched in glucocorticoid receptors (GR) and mineralocorticoid receptors (MR).

Adrenal hypersensitivity precedes chronic hypercorticism in streptozotocin-induced diabetes mice.

Previous studies have demonstrated that type 1 diabetes is characterized by hypercorticism and lack of periodicity in adrenal hormone secretion. In the present study, we tested the hypothesis that hypercorticism is initiated by an enhanced release of ACTH leading subsequently to adrenocortical growth and increased output of adrenocortical hormones. To test this hypothesis, we used the streptozotocin (STZ)-induced diabetes mouse model and measured hypothalamic-pituitary-adrenal axis activity at different time points.

Protective effects of estradiol in the brain of rats with genetic or mineralocorticoid-induced hypertension.

Abnormalities of hippocampus and hypothalamus are commonly observed in rats with genetic (SHR) or mineralocorticoid/salt-induced hypertension. In the hippocampus, changes include decreased cell proliferation in the dentate gyrus (DG), astrogliosis and decreased neuronal density in the hilus, whereas in the hypothalamus expression of arginine vasopressin (AVP) is markedly elevated. Here, we report that estradiol treatment overturns these abnormalities.

Knocking down the diencephalic thyrotropin-releasing hormone precursor gene normalizes obesity-induced hypertension in the rat.

We recently showed that diencephalic TRH may mediate the central leptin-induced pressor effect. Here, to study the role of TRH in obesity-induced hypertension (OIH), we used a model of OIH produced by a high-fat diet (HFD, 45 days) in male Wistar rats. After 4 wk, body weight and systolic arterial blood pressure (SABP) increased in HFD animals.

Estrogens and neuroendocrine hypothalamic-pituitary-adrenal axis function.

The function of the HPA axis is subject to regulation by many factors, which achieve relevance under normal and pathological conditions. In the case of aging, this period of life is associated with disturbances of the HPA axis and signs of hippocampal vulnerability. We examined 20-month-old male rats, in which abnormalities of the HPA axis included altered response to stress, reduced effectiveness of the steroid negative feedback and low expression of hippocampal glucocorticoid receptors (GR).

Hippocampal neuropathology of diabetes mellitus is relieved by estrogen treatment.

1. A recently recognized complication of uncontrolled diabetes mellitus is the encephalopathy involving, among other regions, the hippocampus. Since estrogens bring neuroprotection in cases of brain injury and degenerative diseases, we have studied if estradiol (E2) administration counteracts some hippocampal abnormalities of streptozotocin (STZ)-diabetic adult mice.

Increased astrocyte reactivity in the hippocampus of murine models of type 1 diabetes: the nonobese diabetic (NOD) and streptozotocin-treated mice.

Diabetes can be associated with cerebral dysfunction in humans and animal models of the disease. Moreover, brain anomalies and alterations of the neuroendocrine system are present in type 1 diabetes (T1D) animals, such as the spontaneous nonobese diabetic (NOD) mouse model and/or the pharmacological streptozotocin (STZ)-induced model. Because of the prevalent role of astrocytes in cerebral glucose metabolism and their intimate connection with neurones, we investigated hippocampal astrocyte alterations in prediabetic and diabetic NOD mice and STZ-treated diabetic mice.

Deoxycorticosterone stimulates the activity of nicotinamide adenine dinucleotide phosphate-diaphorase/nitric oxide synthase immunoreactivity in hypothalamic nuclei of rats.

Mineralocorticoids (MC) play an important role in development of salt appetite. Part of this effect involves the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, in which MC treatment increases arginine vasopressin (AVP) synthesis and release. Since the AVP system is also modulated by nitric oxide (NO), we studied if deoxycorticosterone acetate (DOCA) treatment changed the number of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) active neurons and neuronal NO synthase (nNOS)-immunoreactive (IR) cells in the PVN and SON.