Reversal of Age-Related Alterations in Synaptic Plasticity by Blockade of L-Type Ca<sup>2+</sup>Channels

Norris, Christopher M.; Halpain, Shelley; Foster, Thomas C.

doi:10.1523/jneurosci.18-09-03171.1998

Cited by 257 publications

(207 citation statements)

References 54 publications

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“…[79]) This effect of the oxidative stress is Ca 2+ dependent [87,88,91,92,133,134]; a finding consistent with the fact that calcium inhibits synaptic plasticity. It is noteworthy that treatment with n-3 fatty acids can restore the LTP in aged rats [70,71,[77][78][79].…”

Section: Oxidative Stress and Ltpsupporting

confidence: 68%

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Yehuda¹,

Rabinovitz²,

Carasso³

et al. 2002

Neurobiology of Aging

353

200

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In addition to a gradual loss of neurons in various brain regions, major biochemical changes in the brain affect the neuronal membrane that is the "site of action" for many essential functions including long-term potentiation (LTP), learning and memory, sleep, pain threshold, and thermoregulation. Normal physiological functioning includes the transmission of axonal information, regulation of membrane-bound enzymes, control of ionic channels and various receptors. All are highly dependent on membrane fluidity, where rigidity is increased during aging. The significantly higher level of cholesterol in aging neuronal membrane, the slow rate of cholesterol turnover, and the decreased level of total polyunsaturated fatty acids (PUFA) may result from poor passage rate via the blood-brain barrier, or from a decreased rate of incorporation into the membrane, or a decrease in the activities of delta-6 and delta-9 desaturase enzymes. The added oxidative stress, which leads to an increase of free radicals leading to a decrease in membrane fluidity, may respond to a restricted diet, and thereby overcome the damaging effects of the free radicals. A central focus of this review is that a specific ratio of n-3/n-6 PUFA can restore many of these age-related effects.

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Section: Oxidative Stress and Ltpsupporting

confidence: 68%

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Yehuda¹,

Rabinovitz²,

Carasso³

et al. 2002

Neurobiology of Aging

353

200

View full text Add to dashboard Cite

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“…The effects of ageing on hippocampal synaptic plasticity have been studied previously. Significant LTP induction has been shown in rats up to 20±24 months of age, but LTP induction and maintenance in younger animals was easier and proved to be more stable [13,26]. It has been suggested that potentiation deficits in aged rats can only be detected with brief trains of HFS (less than 50 pulses) [27,28].…”

Section: Discussionmentioning

confidence: 99%

“…In experimental models for ageing, as well as in models for diabetes, hippocampal synapses show plasticity modifications favouring LTD induction [11,34,44], whereas LTP expression and maintenance is impaired [11,45]. In ageing rats, it was shown that an increase in Ca 2+ influx through L-type voltagedependent Ca 2+ channels can lower the LTD induction threshold [26]. Moreover, this Ca 2+ influx would also impair LTP induction by the activation of the Ca 2+ -dependent, K-mediated after-hyperpolarisation [26].…”

Section: Discussionmentioning

confidence: 99%

Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: interaction of diabetes and ageing

et al. 2000

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Peripheral neuropathy is a well-known complication of both clinical and experimental diabetes mellitus. Long-term diabetes also leads to a variety of discrete functional and structural disorders in the central nervous system [1]. Moderate impairment of cognitive function has been observed in middle-aged adults with Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus. In the elderly cognitive deficits appear, however, to be more pronounced and can readily be detected with relatively crude tests such as the mini-mental state examination [4,5].The hippocampus is a brain structure involved in certain forms of learning [6,7]. At the cellular level, hippocampal long-term potentiation (LTP) and depression (LTD) are two forms of synaptic plasticity which have attracted considerable attention in the search for the mechanisms of learning and memory [8,9]. We have shown previously that LTP expression was impaired in the CA1 and the CA3 field of the hippocampus of young adult diabetic rats, whereas LTD expression in the CA1 field was enhanced [10, Diabetologia (2000) Abstract Aims/hypothesis. Diabetes mellitus leads to functional and structural changes in the brain which appear to be most pronounced in the elderly. Because the pathogenesis of brain ageing and that of diabetic complications show close analogies, it is hypothesized that the effects of diabetes and ageing on the brain interact. Our study examined the effects of diabetes and ageing on learning and hippocampal synaptic plasticity in rats. Methods. Young adult (5 months) and aged (2 years) rats were examined after 8 weeks of streptozotocindiabetes. Learning was tested in a Morris water maze. Synaptic plasticity was tested ex vivo, in hippocampal slices, in response to trains of stimuli of different frequency (0.05 to 100 Hz). Results. Statiscally significant learning impairments were observed in young adult diabetic rats compared with controls. These impairments were even greater in aged diabetic animals. In hippocampal slices from young adult diabetic animals long-term potentiation induced by 100 Hz stimulation was impaired compared with controls (138 vs 218 % of baseline). In contrast, long-term depression induced by 1 Hz stimulation was enhanced in slices from diabetic rats compared with controls (79 vs 92 %). In non-diabetic aged rats synaptic responses were 149 and 93 % of baseline in response to 100 and 1 Hz stimulation, compared with 106 and 75 % in aged diabetic rats. Conclusion/interpretation. Both diabetes and ageing affect learning and hippocampal synaptic plasticity. The cumulative deficits in learning and synaptic plasticity in aged diabetic rats indicate that the effects of diabetes and ageing on the brain could interact. [Diabetologia (2000) 43: 500±506]

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“…In cultured embryonic hippocampal neurons that are maintained for 28 days, there is an increase in calcium channel activity and in after-hyperpolarization that is accompanied by decreased neuronal survival; blocking L-type calcium channels increased neuronal survival (116). It is interesting to note that the increased after-hyperpolarization is associated with an enhanced induction of long-term depression in CA1 pyramidal neurons and an impaired induction of long-term potentiation (105). Thus, insofar as LTP and LTD may be related to synaptic plasticity during learning (87), these age-related changes suggest a possible basis for cognitive impairment in aging rats (105).…”

Section: Neuron Death Is Not Inevitable Nor the Only Cause Of Age-relmentioning

confidence: 99%

“…It is interesting to note that the increased after-hyperpolarization is associated with an enhanced induction of long-term depression in CA1 pyramidal neurons and an impaired induction of long-term potentiation (105). Thus, insofar as LTP and LTD may be related to synaptic plasticity during learning (87), these age-related changes suggest a possible basis for cognitive impairment in aging rats (105).…”

Section: Neuron Death Is Not Inevitable Nor the Only Cause Of Age-relmentioning

confidence: 99%

Stress and the Aging Hippocampus

McEwen

1999

Frontiers in Neuroendocrinology

208

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The ''glucocorticoid cascade hypothesis'' of hippocampal aging has stimulated a great deal of research into the neuroendocrine aspects of aging and the role of glucocorticoids, in particular. Besides strengthening the methods for investigating the aging brain, this research has revealed that the interactions between glucocorticoids and hippocampal neurons are far more complicated than originally envisioned and involve the participation of neurotransmitter systems, particularly the excitatory amino acids, as well as calcium ions and neurotrophins. New information has provided insights into the role of early experience in determining individual differences in brain and body aging by setting the reactivity of the hypothalamopituitary-adrenal axis and the autonomic nervous system. As a result of this research and advances in neuroscience and the study of aging, we now have a far more sophisticated view of the interactions among genes, early development, and environmental influences, as well as a greater appreciation of events at the cellular and molecular levels which protect neurons, and a greater appreciation of pathways of neuronal damage and destruction. While documenting the ultimate vulnerability of the brain to stressful challenges and to the aging process, the net result of this research has highlighted the resilience of the brain and offered new hope for treatment strategies for promoting the health of the aging brain. KEY WORDS: stress; hippocampal aging; glucocorticoid cascade hypothesis. 1999 Academic Press INTRODUCTIONThe hippocampus is a particularly vulnerable and sensitive region of the brain that is also very important for declarative and spatial learning and memory (36). Hippocampal neurons are vulnerable to seizures, strokes, and head trauma, as well as responding to stressful experiences (27,92,130). At the same time they show remarkable plasticity, involving long-term synaptic potentiation and depression, dendritic remodeling, synaptic turnover, and neurogenesis in the case of the dentate gyrus (Fig 1) (17,27,92).The work of aus der Muhlen and Ockenfels (3) first drew attention to potentially toxic actions of adrenal steroids. The reported darkly stained neurons in the hippocampus of guinea pigs exposed to high levels of glucocorticoids, an observation that has been confirmed and extended to repeated stress in subsequent studies (41,100), although there are still some doubts as to whether ''dark neurons'' may be artifacts of tissue trauma (18). In 1968, we discovered receptors for adrenal steroids in hippocampus (95), and it is now known that two types of adrenal steroid receptors exist in the hippocampus and other brain regions and mediate a variety of adrenal steroid effects on excitability, neurochemistry, and structure (27). Landfield (68) and then Sapolsky (127,128) provided evidence for a role of adrenal steroids in neuronal aging in the hippocampus, leading to the formulation of the ''glucocorticoid cascade hypothesis '' (130). This hypothesis states that glucocorticoids participate in a ...

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Reversal of Age-Related Alterations in Synaptic Plasticity by Blockade of L-Type Ca²⁺Channels

Cited by 257 publications

References 54 publications

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: interaction of diabetes and ageing

Stress and the Aging Hippocampus

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Reversal of Age-Related Alterations in Synaptic Plasticity by Blockade of L-Type Ca2+Channels

Cited by 257 publications

References 54 publications

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: interaction of diabetes and ageing

Stress and the Aging Hippocampus

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Reversal of Age-Related Alterations in Synaptic Plasticity by Blockade of L-Type Ca²⁺Channels