Isaura Tavares

Bio: Isaura Tavares is an academic researcher from University of Porto. The author has contributed to research in topics: Nociception & Spinal cord. The author has an hindex of 30, co-authored 90 publications receiving 3195 citations. Previous affiliations of Isaura Tavares include University of South Carolina & Max Planck Society.

Amidated and Ibuprofen-Conjugated Kyotorphins Promote Neuronal Rescue and Memory Recovery in Cerebral Hypoperfusion Dementia Model.

Abstract: Chronic brain ischemia is a prominent risk factor for neurological dysfunction and progression for dementias, including Alzheimer’s disease (AD). In rats, permanent bilateral common carotid artery occlusion (2VO) causes a progressive neurodegeneration in the hippocampus, learning deficits and memory loss as it occurs in AD. Kyotorphin (KTP) is an endogenous antinociceptive dipeptide whose role as neuromodulator/neuroprotector has been suggested. Recently, we designed two analgesic KTP-derivatives, KTP-amide (KTP-NH2) and KTP-NH2 linked to ibuprofen (IbKTP-NH2) to improve KTP brain targeting. This study investigated the effects of KTP-derivatives on cognitive/behavioral functions (motor/spatial memory/nociception) and hippocampal pathology of female rats in chronic cerebral hypoperfusion (2VO-rat model). 2VO-animals were treated with KTP-NH2 or IbKTP-NH2 for 7 days at weeks 2 and 5 post-surgery. After behavioral testing (week 6), coronal sections of hippocampus were H&E-stained or immunolabeled for the cellular markers GFAP (astrocytes) and NFL (neurons). Our findings show that KTP-derivatives, mainly IbKTP-NH2, enhanced cognitive impairment of 2VO-animals and prevented neuronal damage in hippocampal CA1 subfield, suggesting their potential usefulness for the treatment of dementia.

Increase in GABAergic Cells and GABA Levels in the Spinal Cord in Unilateral Inflammation of the Hindlimb in the Rat.

Abstract: The effects of chronic peripheral inflammation on spinal cord gamma-aminobutyric acid (GABA) were examined in the rat. Following the injection of complete Freund's adjuvant in the left hindlimb footpad an increased number of immunoreactive cells occurred in ipsilateral laminae I - III of the dorsal horn from L3 to L5. GABA-immunoreactive cells were more numerous than contralaterally 1 week after the onset of the inflammation, reached maximal numbers after 3 - 4 weeks, and declined thereafter. Differences from control sides were statistically significant except at week 6. GABA levels in homogenates of the ipsilateral lumbar enlargement were increased significantly at 4 weeks. Since increases in GABA occurred in the spinal cord zone of projection of the nerves supplying the inflamed foot, the central response is surmised to result from the increased nociceptive input arriving from the periphery. However, the transmission from primary axons to GABA interneurons is not likely to be monosynaptic since profiles containing glutamate decarboxylase or GABA immunoreactivity are known to be predominantly presynaptic, and rarely postsynaptic, to primary afferent endings in electron micrographs in the rat. The findings support the function attributed to spinal GABA in modulating nociceptive input at segmental level.

Carrageenan-induced inflammation of the hind foot provokes a rise of GABA-immunoreactive cells in the rat spinal cord that is prevented by peripheral neurectomy or neonatal capsaicin treatment

Abstract: An increase in the number of gamma-aminobutyric acid (GABA)-immunoreactive cells is reported in the superficial dorsal horn of the rat spinal cord upon unilateral inflammation of the hind foot caused by subcutaneous carrageenan injection The rise of GABAergic cells was restricted to the ipsilateral dorsal horn, reaching a peak value of 234% over the contralateral side 4 days after carrageenan injection Sciatic neurectomy or neonatal capsaicin treatment prevented this effect These findings suggest that dorsal horn GABA is up-regulated by the increase of noxious inflow conveyed by unmyelinated C fibers from the inflamed tissues

Neuronal plasticity: increasing the gain in pain.

Abstract: We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.

Gut microbiome alterations in Alzheimer's disease.

Abstract: Alzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.