Estrogen Protects the Inner Retina from Apoptosis and Ischemia-Induced Loss of Vesl-1L/Homer 1c Immunoreactive Synaptic Connections

Kaja, Simon; Yang, Shaohua; Wei, Jiao; Fujitani, Kazuko; Liu, Ran; Brun‐Zinkernagel, Anne‐Marie; Simpkins, James W.; Inokuchi, Kaoru; Koulen, Peter

doi:10.1167/iovs.02-1204

Cited by 76 publications

(77 citation statements)

References 53 publications

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“…Further evidence for a link between hormonal status and risk of microvascular complications associated with type 1 diabetes was provided by a study showing that women with diabetic retinopathy and nephropathy undergo menopause at an earlier age [37]. Several experimental studies have demonstrated a renoprotective role for exogenous oestrogens in models of type 1 diabetic retinopathy and nephropathy [38][39][40]. It is possible that early onset of diabetes impairs the ovarian production of oestrogen, thus becoming permissive for the development of organ complications later in life.…”

Section: Discussionmentioning

confidence: 99%

Age at menarche and the risk of diabetic microvascular complications in patients with type 1 diabetes

2015

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Aims/hypothesis The aim of this study was to evaluate the relationship among age at onset of diabetes, age at onset of menarche and risk of diabetic nephropathy and laser-treated retinopathy in type 1 diabetes. Methods Data related to age at menarche were collected through questionnaires and were available for 1,304 women who participated in the Finnish Diabetic Nephropathy Study (FinnDiane). A possible association between age at menarche and diabetic nephropathy and retinopathy was investigated. Results There was an inverse relationship between the age at onset of diabetes and age at menarche: the younger the age at onset of diabetes, the higher the age at menarche (p<0.0001). A non-linear relationship between the age of menarche and risk of diabetic microvascular complications was found in patients with diabetes onset before menarche, but there was no such association in patients with diabetes onset after menarche. Women with delayed menarche (> mean age+2 years) had a 2.30 (95% CI 1.27, 4.17; p<0.006) times higher risk of nephropathy compared with the women who underwent menarche at the mean age±2 years. Delayed menarche also increased the risk of retinopathy (OR 2.34 [95% CI 1.36, 4.01]). After excluding patients with nephropathy, the OR for retinopathy was 2.11 (95% CI 1.15, 3.90). Earlier menarche (< mean age−2 years) did not have any effect on this risk. Conclusions/interpretation Delayed menarche was associated with an increased risk of diabetic nephropathy and retinopathy, whereas early menarche was not. Delayed menarche may be used as a new tool to identify women at risk of diabetic microvascular complications.

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Section: Discussionmentioning

confidence: 99%

Age at menarche and the risk of diabetic microvascular complications in patients with type 1 diabetes

2015

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“…In addition to these limbo-corticostriatal structures, all three Homer isoforms are located within cerebellum [106] and while the expression of Homer3 within the olfactory bulbs is developmentally down-regulated, the expression of both Homer1 and Homer2 isoforms persist throughout development [106]. Within neurons, Homer proteins are localized predominantly in the soma and apical dendrites [102,105,144,158]. At a subcellular level, Homer proteins are enriched within the postsynaptic density (PSD) fraction, but are also present in the crude nuclear, synaptosomal and microsomal fractions [105,144].…”

Section: Homers Are Regulated Within Addiction-related Neural Circuitmentioning

confidence: 99%

Homers regulate drug-induced neuroplasticity: Implications for addiction

Szumlinski

Ary

Lominac

2008

Biochemical Pharmacology

118

160

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Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.

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“…Specifically, we have previously described loss of Vesl-1L/Homer-1c as biomarker for synaptic changes after injury in the retina (Kaja et al 2003), and experimental down-regulation of Homer1b/c has been shown to attenuate glutamate-mediated toxicity in cortical neurons in vitro (Chen et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Homer-1a immediate early gene expression correlates with better cognitive performance in aging

Kaja

Sumien

Borden

et al. 2012

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The molecular mechanisms underlying cognitive decline during healthy aging remain largely unknown. Utilizing aged wild-type C57BL/6 mice as a model for normal aging, we tested the hypothesis that cognitive performance, memory, and learning as assessed in established behavioral testing paradigms are correlated with the differential expression of isoforms of the Homer family of synaptic scaffolding proteins. Here we describe a loss of cognitive and motor function that occurs when Homer-1a/Vesl-1S protein levels drop during aging. Our data describe a novel mechanism of age-related synaptic changes contributing to loss of biological function, spatial learning, and memory formation as well as motor coordination, with the dominant negative uncoupler of synaptic protein clustering, Homer-1a/Vesl-1S, as a potential target for the prophylaxis and treatment of age-related cognitive decline.

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Estrogen Protects the Inner Retina from Apoptosis and Ischemia-Induced Loss of Vesl-1L/Homer 1c Immunoreactive Synaptic Connections

Cited by 76 publications

References 53 publications

Age at menarche and the risk of diabetic microvascular complications in patients with type 1 diabetes

Age at menarche and the risk of diabetic microvascular complications in patients with type 1 diabetes

Homers regulate drug-induced neuroplasticity: Implications for addiction

Homer-1a immediate early gene expression correlates with better cognitive performance in aging

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