Bmc Neurosci
-
Low-intensity transcranial focused ultrasound (tFUS) has emerged as a new non-invasive modality of brain stimulation with the potential for high spatial selectivity and penetration depth. Anesthesia is typically applied in animal-based tFUS brain stimulation models; however, the type and depth of anesthesia are known to introduce variability in responsiveness to the stimulation. Therefore, the ability to conduct sonication experiments on awake small animals, such as rats, is warranted to avoid confounding effects of anesthesia. ⋯ The wearable miniature tFUS configuration allowed for the stimulation of motor cortical areas in rats and elicited sonication-related movements under both awake and anesthetized conditions. The awake condition yielded diverse physical responses compared to those reported in existing literatures. The ability to conduct an experiment in freely-moving awake animals can be gainfully used to investigate the effects of acoustic neuromodulation free from the confounding effects of anesthesia, thus, may serve as a translational platform to large animals and humans.
-
Transcranial focused ultrasound (tFUS) is a new non-invasive neuromodulation technique that uses mechanical energy to modulate neuronal excitability with high spatial precision. tFUS has been shown to be capable of modulating EEG brain activity in humans that is spatially restricted, and here, we use 7T MRI to extend these findings. We test the effect of tFUS on 7T BOLD fMRI signals from individual finger representations in the human primary motor cortex (M1) and connected cortical motor regions. Participants (N = 5) performed a cued finger tapping task in a 7T MRI scanner with their thumb, index, and middle fingers to produce a BOLD signal for individual M1 finger representations during either tFUS or sham neuromodulation to the thumb representation. ⋯ Single element tFUS can be paired with high field MRI that does not induce significant artifact. tFUS increases activation volumes of the targeted finger representation that is spatially restricted within M1 but does not extend to functionally connected motor regions. Trial registration ClinicalTrials.gov NCT03634631 08/14/18.
-
Alzheimer's disease (AD), the most common cause of dementia, is characterized by the progressive deposition of amyloid-β (Aβ) peptides and neurofibrillary tangles. Mouse models of Aβ amyloidosis generated by knock-in (KI) of a humanized Aβ sequence provide distinct advantages over traditional transgenic models that rely on overexpression of amyloid precursor protein (APP). In App-KI mice, three familial AD-associated mutations were introduced into the endogenous mouse App locus to recapitulate Aβ pathology observed in AD: the Swedish (NL) mutation, which elevates total Aβ production; the Beyreuther/Iberian (F) mutation, which increases the Aβ42/Aβ40 ratio; and the Arctic (G) mutation, which promotes Aβ aggregation. AppNL-G-F mice harbor all three mutations and develop progressive Aβ amyloidosis and neuroinflammatory response in broader brain areas, whereas AppNL mice carrying only the Swedish mutation exhibit no overt AD-related pathological changes. To identify behavioral alterations associated with Aβ pathology, we assessed emotional and cognitive domains of AppNL-G-F and AppNL mice at different time points, using the elevated plus maze, contextual fear conditioning, and Barnes maze tasks. ⋯ AppNL/NL and AppNL-G-F/NL-G-F mice exhibit behavioral changes associated with non-cognitive, emotional domains before the onset of definitive cognitive deficits. Our observations consistently indicate that AppNL-G-F/NL-G-F mice represent a model for preclinical AD. These mice are useful for the study of AD prevention rather than treatment after neurodegeneration.
-
Although amyloid beta (Aβ) imaging is widely used for diagnosing and monitoring Alzheimer's disease in clinical fields, paralleling comparison between 18F-flutemetamol and 18F-florbetaben was rarely attempted in AD mouse model. We performed a comparison of Aβ PET images between 18F-flutemetamol and 18F-florbetaben in a recently developed APPswe mouse model, C57BL/6-Tg (NSE-hAPPsw) Korl. ⋯ Compared with 18F-flutemetamol images, 18F-florbetaben images showed prominent visual uptake intensity, SUVR, and higher correlations with the pathology. In contrast, 18F-flutemetamol was more actively metabolized than was 18F-florbetaben (Son et al. in J Nucl Med 58(Suppl 1):S278, 2017].
-
Post-traumatic stress disorder (PTSD) is an important psychological disease that can develop following the physical experience or witnessing of traumatic events. The psychopathological response to traumatic stressors increases inflammation in the hippocampus and induces memory deficits. Melatonin (MTG) plays critical roles in circadian rhythm disorders, Alzheimer's disease, and other neurological disorders. However, the cognitive efficiency of MTG and its mechanisms of action in the treatment of PTSD remain unclear. Thus, the present study investigated the effects of MTG on spatial cognitive impairments stimulated by single prolonged stress (SPS) in rats, an animal model of PTSD. Male rats received intraperitoneal (i.p.) administration of various doses of MTG for 21 consecutive days after the SPS procedure. ⋯ The present results indicate that MTG can be beneficial for SPS-stimulated memory impairments via changes in CREB expression and proinflammatory mediators. Thus, MTG may be a prophylactic strategy for the prevention or mitigation of the progression of some features of the PTSD pathology.