Lycorine improves peripheral nerve function by promoting Schwann cell autophagy via AMPK pathway activation and MMP9 downregulation in diabetic peripheral neuropathy

AbstractImpaired postural control is often observed in response to neurotoxic chemotherapy. However, potential explanatory factors other than chemotherapy-induced peripheral neuropathy (CIPN) have not been adequately considered to date due to primarily cross-sectional study designs. Our objective was to comprehensively analyze postural control during and after neurotoxic chemotherapy, and to identify potential CIPN-independent predictors for its impairment. Postural control and CIPN symptoms (EORTC QLQ-CIPN20) were longitudinally assessed before, during and three weeks after neurotoxic chemotherapy, and in three and six months follow-up examinations (N = 54). The influence of peripheral nerve function as determined by nerve conduction studies (NCS: compound motor action potentials (CMAP) and sensory action potentials (SNAP)), physical activity, and muscle strength on the change in postural control during and after chemotherapy was analyzed by multiple linear regression adjusted for age and body mass index. Postural control, CIPN signs/symptoms, and CMAP/SNAP amplitudes significantly deteriorated during chemotherapy (p < .01). During follow-up, patients recovered from postural instabilities (p < .01), whereas CIPN signs/symptoms and pathologic NCS findings persisted compared to baseline (p < .001). The regression model showed that low CMAP and high SNAP amplitudes at baseline predicted impairment of postural control during but not after chemotherapy. Hence, pre-therapeutically disturbed somatosensory inputs may induce adaptive processes that have compensatory effects and allow recovery of postural control while CIPN signs/symptoms and pathologic peripheral nerve function persist. Baseline NCS findings in cancer patients who receive neurotoxic chemotherapy thus might assist in delineating individual CIPN risk profiles more precisely to which specific exercise intervention programs could be tailor-made.

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Schwann Cell Mitochondrial Metabolism Supports Long-Term Axonal Survival and Peripheral Nerve Function

Journal of Neuroscience ◽

10.1523/jneurosci.0884-11.2011 ◽

2011 ◽

Vol 31 (28) ◽

pp. 10128-10140 ◽

Cited By ~ 92

Author(s):

A. Viader ◽

J. P. Golden ◽

R. H. Baloh ◽

R. E. Schmidt ◽

D. A. Hunter ◽

...

Keyword(s):

Schwann Cell ◽

Peripheral Nerve ◽

Mitochondrial Metabolism ◽

Nerve Function ◽

Peripheral Nerve Function

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Association of integrin beta-3 polymorphism and chronic oxaliplatin-induced peripheral neuropathy: Preliminary results

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15082 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15082-e15082

Author(s):

A. Antonacopoulou ◽

A. Argyriou ◽

A. E. Kottorou ◽

C. D. Scopa ◽

H. P. Kalofonos

Keyword(s):

Peripheral Neuropathy ◽

Peripheral Nerve ◽

Nerve Function ◽

Clinical Issue ◽

Chain Reactions ◽

Polymerase Chain Reactions ◽

Adhesion Ability ◽

Peripheral Nerve Function ◽

Integrin Beta 3 ◽

Erk2 Activation

e15082 Background: Peripheral neuropathy (PN) is widely recognised among the major non-haematological dose- limiting toxicities of oxaliplatin (OXL) which is used to treat advanced or metastatic colorectal cancer (CRC). OXL induces two clinically distinct forms of PN. The acute transient syndrome and the chronic OXL-induced peripheral neuropathy (OXLIPN). The integrin beta-3 (ITGB3) polymorphism at residue 33 (L33P) has been previously associated with altered adhesion ability and ERK2 activation. Thus it may affect neuronal survival. The aim of the current study was to investigate the role of the ITGB3 polymorphism at residue 33 in the development of chronic OXLIPN. Methods: Thirty four patients with advanced CRC were genotyped. All patients, 22 males and 12 females had received adjuvant chemotherapy consisting of 12 courses of the formal FOLFOX-4 regimen. Following the discontinuation of treatment, 20 of the patients (58.8 %), developed OXLIPN, whereas the remaining 14 (41.2%) patients remained unaffected with normal peripheral nerve function. The grading of the OXLIPN severity was defined by Total Neuropathy scores, corresponding to the WHO grading scales 1–3 for chemotherapy-induced PN. Genotyping was performed using allele specific primers and sybr green in real time polymerase chain reactions. Statistics were performed using the SPSS for Windows (release 16.0). Results: Patients with normal peripheral nerve function OXLIPN were 14.3% homozygous for C, 28.6% heterozygous and 57.1% homozygous for T. The corresponding percentages for patients who developed OXLIPN did not differ significantly and were 5%, 25% and 70%, respectively. The majority of patients with mild OXLIPN were heterozygotes (50%, with 16.7% CC and 33.3% TT), whereas the majority of patients with moderate OXLIPN were homozygous for TT (85.7% with the remaining 14.3% being CT). Notably, the TT genotype was associated with increased OXLIPN compared to the genotypes containing the C allele (p= 0.046). Conclusions: The ITGB3 polymorphism at residue 33 appears to be unrelated to the development of OXLIPN but related to the grade of OXLIPN.Further study on this important clinical issue is warranted. No significant financial relationships to disclose.

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