Brain derived neurotrophic factor (BDNF) release from the human brain in patients with type 2 diabetes—possible influence of venous anatomy and comorbid major depressive disorder

Lambert, Gavin; Schlaich, Markus P.; Esler, Murray

doi:10.1007/s00125-007-0756-3

Cited by 11 publications

(9 citation statements)

References 8 publications

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“…Our findings also may be consistent with the clinical disease literature. Cerebral output and plasma levels of BDNF are reduced in individuals with type 2 diabetes (48–50). Because these changes occur in an insulin-dependent manner, it suggests that glycemic memory and BDNF status might be linked (49).…”

Section: Discussionmentioning

confidence: 99%

Decreased Cerebrovascular Brain-Derived Neurotrophic Factor–Mediated Neuroprotection in the Diabetic Brain

et al. 2011

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OBJECTIVEDiabetes is an independent risk factor for stroke. However, the underlying mechanism of how diabetes confers that this risk is not fully understood. We hypothesize that secretion of neurotrophic factors by the cerebral endothelium, such as brain-derived neurotrophic factor (BDNF), is suppressed in diabetes. Consequently, such accrued neuroprotective deficits make neurons more vulnerable to injury.RESEARCH DESIGN AND METHODSWe examined BDNF protein levels in a streptozotocin-induced rat model of diabetes by Western blotting and immunohistochemistry. Levels of total and secreted BDNF protein were quantified in human brain microvascular endothelial cells after exposure to advanced glycation end product (AGE)-BSA by enzyme-linked immunosorbent assay and immunocytochemistry. In media transfer experiments, the neuroprotective efficacy of conditioned media from normal healthy endothelial cells was compared with AGE-treated endothelial cells in an in vitro hypoxic injury model.RESULTSCerebrovascular BDNF protein was reduced in the cortical endothelium in 6-month diabetic rats. Immunohistochemical analysis of 6-week diabetic brain sections showed that the reduction of BDNF occurs early after induction of diabetes. Treatment of brain microvascular endothelial cells with AGE caused a similar reduction in BDNF protein and secretion in an extracellular signal–related kinase-dependent manner. In media transfer experiments, conditioned media from AGE-treated endothelial cells were less neuroprotective against hypoxic injury because of a decrease in secreted BDNF.CONCLUSIONSTaken together, our findings suggest that a progressive depletion of microvascular neuroprotection in diabetes elevates the risk of neuronal injury for a variety of central nervous system diseases, including stroke and neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Decreased Cerebrovascular Brain-Derived Neurotrophic Factor–Mediated Neuroprotection in the Diabetic Brain

et al. 2011

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“…We did not determine the lactate/pyruvate ratio and are unaware of the potential effect of glycopyrrolate on these variables, but we would consider the effect of glycopyrrolate to be minimal because glycopyrrolate did not affect arterial lactate concentrations during exercise. We also consider that the estimation of changes in global CBF from the jugular venous oxygen content is complicated by the asymmetrical drainage of the cerebral venous sinuses (Lambert et al 2007) and, notably, by the fact that the internal jugular vein collapses in the upright posture. Since the subjects performed handgrip exercise in a semi-recumbent position, changes in jugular venous outflow may not be representative of the global change.…”

Section: Limitationsmentioning

confidence: 99%

Experimental Physiology –Research Paper: Glycopyrrolate abolishes the exercise‐induced increase in cerebral perfusion in humans

Seifert

Fisher

Young

et al. 2010

Experimental Physiology

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Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exerciseinduced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral metabolism (from arterial and internal jugular venous O 2 , glucose and lactate differences), as well as the middle cerebral artery mean blood velocity (MCA V mean ; transcranial Doppler ultrasound) during a sustained static handgrip contraction at 40% of maximal voluntary contraction (n = 9) and the MCA V mean during ergometer cycling (n = 8). Separate, randomized and counterbalanced trials were performed in control (no drug) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate. Glycopyrrolate increased resting heart rate from ∼60 to ∼110 beats min −1 (P < 0.01) and cardiac output by ∼40% (P < 0.05), but did not affect mean arterial pressure. The central cardiovascular responses to exercise with glycopyrrolate were similar to the control responses, except that cardiac output did not increase during static handgrip with glycopyrrolate. Glycopyrrolate did not significantly affect cerebral metabolism during static handgrip, but a parallel increase in MCA V mean (∼16%; P < 0.01) and CBF (∼12%; P < 0.01) during static handgrip, as well as the increase in MCA V mean during cycling (∼15%; P < 0.01), were abolished by glycopyrrolate (P < 0.05). Thus, during both cycling and static handgrip, a cholinergic receptor mechanism is important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen.

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“…There is study that suggests that depression in diabetes may disturb the balance of brain-derived neurotrophic factor (BDNF), causing cognitive decline or dementia [86]. Another study found that cerebrovascular risk factors were significant predictors of depression in diabetic patients [87], suggesting that depression-related cognitive deficits may be the result of cerebrovascular diseases.…”

Section: Cognitive Impairments and Diabetes Mellitusmentioning

confidence: 99%

Diabetes Cognitive Impairments and the Effect of Traditional Chinese Herbs

Guo

Tian

2013

Evidence-Based Complementary and Alternative Medicine

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The problem of cognitive impairment resulting from diabetes is gaining more acceptance and attention. Both type 1 and type 2 diabetes mellitus have been proved to be associated with reduced performance on numerous domains of cognitive function. Although the exact mechanisms of cognitive impairments in diabetes have not been completely understood, hyperglycemia and insulin resistance seem to play significant roles. And other possible risk factors such as hypoglycemia, insulin deficiency, vascular risk factors, hyperactive HPA axis, depression, and altered neurotransmitters will also be examined. In the meanwhile, this review analyzed the role of the active ingredient of Chinese herbal medicine in the treatment of diabetes cognitive impairments.

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Brain derived neurotrophic factor (BDNF) release from the human brain in patients with type 2 diabetes—possible influence of venous anatomy and comorbid major depressive disorder

Cited by 11 publications

References 8 publications

Decreased Cerebrovascular Brain-Derived Neurotrophic Factor–Mediated Neuroprotection in the Diabetic Brain

Decreased Cerebrovascular Brain-Derived Neurotrophic Factor–Mediated Neuroprotection in the Diabetic Brain

Experimental Physiology –Research Paper: Glycopyrrolate abolishes the exercise‐induced increase in cerebral perfusion in humans

Diabetes Cognitive Impairments and the Effect of Traditional Chinese Herbs

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