Neurogenesis in the adult brain functionally contributes to the maintenance of chronic neuropathic pain

Tan, Linette Liqi; Alfonso, Julieta; Monyer, Hannah; Kuner, Rohini

doi:10.1038/s41598-021-97093-x

Cited by 4 publications

(4 citation statements)

References 44 publications

(52 reference statements)

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“…Perhaps surprisingly, both adult neurogenesis and neuroplasticity have been reported to contribute to the maintenance of long-lasting NP (i.e., chronicity) [ 52 ] and NP that may occur adjacent to or remotely from any injury site [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of microRNAs in Serum of Patients with Chronic Painful Polyneuropathy and Healthy Age-Matched Controls

et al. 2023

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Polyneuropathies (PNP) are the most common type of disorder of the peripheral nervous system in adults. However, information on microRNA expression in PNP is lacking. Following microRNA sequencing, we compared the expression of microRNAs in the serum of patients experiencing chronic painful PNP with healthy age-matched controls. We have been able to identify four microRNAs (hsa-miR-3135b, hsa-miR-584-5p, hsa-miR-12136, and hsa-miR-550a-3p) that provide possible molecular links between degenerative processes, blood flow regulation, and signal transduction, that eventually lead to PNP. In addition, these microRNAs are discussed regarding the targeting of proteins that are involved in high blood flow/pressure and neural activity dysregulations/disbalances, presumably resulting in PNP-typical symptoms such as chronical numbness/pain. Within our study, we have identified four microRNAs that may serve as potential novel biomarkers of chronic painful PNP, and that may potentially bear therapeutic implications.

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Section: Discussionmentioning

confidence: 99%

Differential Expression of microRNAs in Serum of Patients with Chronic Painful Polyneuropathy and Healthy Age-Matched Controls

et al. 2023

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“…However, the scope of these studies primarily focused on short‐term evaluations of cell proliferation. Due to the tightly regulated nature of the neurogenic cascade, exposure to the ischemia and other adverse environment can lead to several adverse outcomes, including increased neuroblast loss and decreased survival of newly formed mature neurons in the granular layers of the hippocampus 56,57 . In fact, it has been proposed that maladaptive neurogenesis could, in certain instances, contribute to the progression of brain dysfunction 58 .…”

Section: Discussionmentioning

confidence: 99%

“…Due to the tightly regulated nature of the neurogenic cascade, exposure to the ischemia and other adverse environment can lead to several adverse outcomes, including increased neuroblast loss and decreased survival of newly formed mature neurons in the granular layers of the hippocampus. 56 , 57 In fact, it has been proposed that maladaptive neurogenesis could, in certain instances, contribute to the progression of brain dysfunction. 58 Evaluating whether neurogenesis produces mature neurons and integrates into neural circuits to ameliorate behavioral deficits is of utmost importance.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF/TrkB/CREB signaling pathway in hypoxic–ischemic neonatal rats

Chen,

Wei

et al. 2023

CNS Neurosci Ther

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AimsDexmedetomidine (DEX) has been reported to alleviate hypoxic–ischemic brain damage (HIBD) in neonates. This study aimed to investigate whether DEX improves cognitive impairment by promoting hippocampal neurogenesis via the BDNF/TrkB/CREB signaling pathway in neonatal rats with HIBD.MethodsHIBD was induced in postnatal day 7 rats using the Rice‐Vannucci method, and DEX (25 μg/kg) was administered intraperitoneally immediately after the HIBD induction. The BDNF/TrkB/CREB pathway was regulated by administering the TrkB receptor antagonist ANA‐12 through intraperitoneal injection or by delivering adeno‐associated virus (AAV)‐shRNA‐BDNF via intrahippocampal injection. Western blot was performed to measure the levels of BDNF, TrkB, and CREB. Immunofluorescence staining was utilized to identify the polarization of astrocytes and evaluate the levels of neurogenesis in the dentate gyrus of the hippocampus. Nissl and TTC staining were performed to evaluate the extent of neuronal damage. The MWM test was conducted to evaluate spatial learning and memory ability.ResultsThe levels of BDNF and neurogenesis exhibited a notable decrease in the hippocampus of neonatal rats after HIBD, as determined by RNA‐sequencing technology. Our results demonstrated that treatment with DEX effectively increased the protein expression of BDNF and the phosphorylation of TrkB and CREB, promoting neurogenesis in the dentate gyrus of the hippocampus in neonatal rats with HIBD. Specifically, DEX treatment significantly augmented the expression of BDNF in hippocampal astrocytes, while decreasing the proportion of detrimental A1 astrocytes and increasing the proportion of beneficial A2 astrocytes in neonatal rats with HIBD. Furthermore, inhibiting the BDNF/TrkB/CREB pathway using either ANA‐12 or AAV‐shRNA‐BDNF significantly counteracted the advantageous outcomes of DEX on hippocampal neurogenesis, neuronal survival, and cognitive improvement.ConclusionsDEX promoted neurogenesis in the hippocampus by activating the BDNF/TrkB/CREB pathway through the induction of polarization of A1 astrocytes toward A2 astrocytes, subsequently mitigating neuronal damage and cognitive impairment in neonates with HIBD.

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“…Notably, depression is highly prevalent among patients with rheumatoid arthritis (or chronic pain), and it is also associated with poorer clinical outcomes [ 38 , 39 ]. Finally, a very recent publication demonstrated that adult hippocampal neurogenesis is involved in the maintenance of pathological pain induced by peripheral neuropathy [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

Experimental Arthritis Inhibits Adult Hippocampal Neurogenesis in Mice

Rusznák

Horváth

Pohli-Tóth

et al. 2022

Cells

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Background: Adult-born neurons of the hippocampal dentate gyrus play a role in specific forms of learning, and disturbed neurogenesis seems to contribute to the development of neuropsychiatric disorders, such as major depression. Neuroinflammation inhibits adult neurogenesis, but the effect of peripheral inflammation on this form of neuroplasticity is ambiguous. Objective: Our aim was to investigate the influence of acute and chronic experimental arthritis on adult hippocampal neurogenesis and to elucidate putative regulatory mechanisms. Methods: Arthritis was triggered by subcutaneous injection of complete Freund’s adjuvant (CFA) into the hind paws of adult male mice. The animals were killed either seven days (acute inflammation) or 21 days (chronic inflammation) after the CFA injection. Behavioral tests were used to demonstrate arthritis-related hypersensitivity to painful stimuli. We used in vivo bioluminescence imaging to verify local inflammation. The systemic inflammatory response was assessed by complete blood cell counts and by measurement of the cytokine/chemokine concentrations of TNF-α, IL-1α, IL-4, IL-6, IL-10, KC and MIP-2 in the inflamed hind limbs, peripheral blood and hippocampus to characterize the inflammatory responses in the periphery and in the brain. In the hippocampal dentate gyrus, the total number of newborn neurons was determined with quantitative immunohistochemistry visualizing BrdU- and doublecortin-positive cells. Microglial activation in the dentate gyrus was determined by quantifying the density of Iba1- and CD68-positive cells. Results: Both acute and chronic arthritis resulted in paw edema, mechanical and thermal hyperalgesia. We found phagocytic infiltration and increased levels of TNF-α, IL-4, IL-6, KC and MIP-2 in the inflamed hind paws. Circulating neutrophil granulocytes and IL-6 levels increased in the blood solely during the acute phase. In the dentate gyrus, chronic arthritis reduced the number of doublecortin-positive cells, and we found increased density of CD68-positive macrophages/microglia in both the acute and chronic phases. Cytokine levels, however, were not altered in the hippocampus. Conclusions: Our data suggest that acute peripheral inflammation initiates a cascade of molecular and cellular changes that eventually leads to reduced adult hippocampal neurogenesis, which was detectable only in the chronic inflammatory phase.

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Neurogenesis in the adult brain functionally contributes to the maintenance of chronic neuropathic pain

Cited by 4 publications

References 44 publications

Differential Expression of microRNAs in Serum of Patients with Chronic Painful Polyneuropathy and Healthy Age-Matched Controls

Differential Expression of microRNAs in Serum of Patients with Chronic Painful Polyneuropathy and Healthy Age-Matched Controls

Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF/TrkB/CREB signaling pathway in hypoxic–ischemic neonatal rats

Experimental Arthritis Inhibits Adult Hippocampal Neurogenesis in Mice

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